The hypothalamus is a part of the brain located superior and anterior to the brain stem and inferior to the thalamus. It serves many different functions in the nervous system, and is also responsible for the direct control of the endocrine system through the pituitary gland. The hypothalamus contains special cells called neurosecretory cells—neurons that secrete hormones:

· Thyrotropin-releasing hormone (TRH)

· Growth hormone-releasing hormone (GHRH)

· Growth hormone-inhibiting hormone (GHIH)

· Gonadotropin-releasing hormone (GnRH)

· Corticotropin-releasing hormone (CRH)

· Oxytocin

· Antidiuretic hormone (ADH)

All of the releasing and inhibiting hormones affect the function of the anterior pituitary gland. TRH stimulates the anterior pituitary gland to release thyroid-stimulating hormone. GHRH and GHIH work to regulate the release of growth hormone—GHRH stimulates growth hormone release, GHIH inhibits its release. GnRH stimulates the release of follicle stimulating hormone and luteinizing hormone while CRH stimulates the release of adrenocorticotropic hormone. The last two hormones—oxytocin and antidiuretic hormone—are produced by the hypothalamus and transported to the posterior pituitary, where they are stored and later released.

Pituitary Gland

The pituitary gland, also known as the hypophysis, is a small pea-sized lump of tissue connected to the inferior portion of the hypothalamus of the brain. Many blood vessels surround the pituitary gland to carry the hormones it releases throughout the body. Situated in a small depression in the sphenoid bone called the sella turcica, the pituitary gland is actually made of 2 completely separate structures: the posterior and anterior pituitary glands.

1. Posterior Pituitary: The posterior pituitary gland is actually not glandular tissue at all, but nervous tissue instead. The posterior pituitary is a small extension of the hypothalamus through which the axons of some of the neurosecretory cells of the hypothalamus extend. These neurosecretory cells create 2 hormones in the hypothalamus that are stored and released by the posterior pituitary:

o Oxytocin triggers uterine contractions during childbirth and the release of milk during breastfeeding.

o Antidiuretic hormone (ADH) prevents water loss in the body by increasing the re-uptake of water in the kidneys and reducing blood flow to sweat glands.

2. Anterior Pituitary: The anterior pituitary gland is the true glandular part of the pituitary gland. The function of the anterior pituitary gland is controlled by the releasing and inhibiting hormones of the hypothalamus. The anterior pituitary produces 6 important hormones:

o Thyroid stimulating hormone (TSH), as its name suggests, is a tropic hormone responsible for the stimulation of the thyroid gland.

o Adrenocorticotropic hormone (ACTH) stimulates the adrenal cortex, the outer part of the adrenal gland, to produce its hormones.

o Follicle stimulating hormone (FSH) stimulates the follicle cells of the gonads to produce gametes—ova in females and sperm in males.

o Luteinizing hormone (LH) stimulates the gonads to produce the sex hormones—estrogens in females and testosterone in males.

o Human growth hormone (HGH) affects many target cells throughout the body by stimulating their growth, repair, and reproduction.

o Prolactin (PRL) has many effects on the body, chief of which is that it stimulates the mammary glands of the breast to produce milk.

Pineal Gland

The pineal gland is a small pinecone-shaped mass of glandular tissue found just posterior to the thalamus of the brain. The pineal gland produces the hormone melatonin that helps to regulate the human sleep-wake cycle known as the circadian rhythm. The activity of the pineal gland is inhibited by stimulation from the photoreceptors of the retina. This light sensitivity causes melatonin to be produced only in low light or darkness. Increased melatonin production causes humans to feel drowsy at nighttime when the pineal gland is active.

Thyroid Gland

The thyroid gland is a butterfly-shaped gland located at the base of the neck and wrapped around the lateral sides of the trachea. The thyroid gland produces 3 major hormones:

· Calcitonin

· Triiodothyronine (T3)

· Thyroxine (T4)

Calcitonin is released when calcium ion levels in the blood rise above a certain set point. Calcitonin functions to reduce the concentration of calcium ions in the blood by aiding the absorption of calcium into the matrix of bones. The hormones T3 and T4 work together to regulate the body’s metabolic rate. Increased levels of T3 and T4 lead to increased cellular activity and energy usage in the body.

Parathyroid Glands

The parathyroid glands are 4 small masses of glandular tissue found on the posterior side of the thyroid gland. The parathyroid glands produce the hormone parathyroid hormone (PTH), which is involved in calcium ion homeostasis. PTH is released from the parathyroid glands when calcium ion levels in the blood drop below a set point. PTH stimulates the osteoclasts to break down the calcium containing bone matrix to release free calcium ions into the bloodstream. PTH also triggers the kidneys to return calcium ions filtered out of the blood back to the bloodstream so that it is conserved.

Adrenal Glands

The adrenal glands are a pair of roughly triangular glands found immediately superior to the kidneys. The adrenal glands are each made of 2 distinct layers, each with their own unique functions: the outer adrenal cortex and inner adrenal medulla.

· Adrenal cortex: The adrenal cortex produces many cortical hormones in 3 classes: glucocorticoids, mineralocorticoids, and androgens.

1. Glucocorticoids have many diverse functions, including the breakdown of proteins and lipids to produce glucose. Glucocorticoids also function to reduce inflammation and immune response.

2. Mineralocorticoids, as their name suggests, are a group of hormones that help to regulate the concentration of mineral ions in the body.

3. Androgens, such as testosterone, are produced at low levels in the adrenal cortex to regulate the growth and activity of cells that are receptive to male hormones. In adult males, the amount of androgens produced by the testes is many times greater than the amount produced by the adrenal cortex, leading to the appearance of male secondary sex characteristics.

· Adrenal medulla: The adrenal medulla produces the hormones epinephrine and norepinephrine under stimulation by the sympathetic division of the autonomic nervous system. Both of these hormones help to increase the flow of blood to the brain and muscles to improve the “fight-or-flight” response to stress. These hormones also work to increase heart rate, breathing rate, and blood pressure while decreasing the flow of blood to and function of organs that are not involved in responding to emergencies.

Pancreas

The pancreas is a large gland located in the abdominal cavity just inferior and posterior to the stomach. The pancreas is considered to be a heterocrine gland as it contains both endocrine and exocrine tissue. The endocrine cells of the pancreas make up just about 1% of the total mass of the pancreas and are found in small groups throughout the pancreas called islets of Langerhans. Within these islets are 2 types of cells—alpha and beta cells. The alpha cells produce the hormone glucagon, which is responsible for raising blood glucose levels. Glucagon triggers muscle and liver cells to break down the polysaccharide glycogen to release glucose into the bloodstream. The beta cells produce the hormone insulin, which is responsible for lowering blood glucose levels after a meal. Insulin triggers the absorption of glucose from the blood into cells, where it is added to glycogen molecules for storage.

Physically, the pancreas is located in the upper abdominal cavity, towards the back — in the C curve of the duodenum. It is about 12 inches long and tapers from right to left. (Remember, anatomically speaking, left and right are referenced from behind the body so they are actually reversed in most diagrams that view the body from the front.) The thick part, the head, comprises almost 50% of the mass of the pancreas and lies to the right, nestled in the C-curve of the duodenum. As for the body of the pancreas, it moves up and to the left, tapering into what is known as the tail of the pancreas, which terminates at the junction of the spleen.

As might be suspected for such an important organ, the pancreas is richly supplied with arteries and veins. It is served by branches from the hepatic artery, the gastroduodenal artery, the pancreaticoduodenal artery, the superior mesenteric artery, and the splenic artery.

Ninety-nine percent of the pancreas is made of acini, clusters of cells that resemble a many-lobed “berry” (acinus is Latin for berry). The acini produce exocrine digestive juices that flow out of the acini through small ducts that eventually join together and feed into the duodenum through the pancreatic duct. But today, we are not interested in that ninety-nine percent. We are interested in the one percent of the pancreas that is made up of several million cells scattered throughout the pancreas, grouped together in globules known as islets of Langerhans. It is these cells that contain the endocrine functioning of the pancreas. A healthy human pancreas contains about one million such globules, which are distributed throughout the organ like tiny islets in a vast ocean of acini — hence their name. Their combined mass is a mere 1 to 1.5 grams.

Physiology of the endocrine pancreas — four cell types

A single islet of Langerhans is actually comprised of four distinct types of cells (alpha, beta, delta, and gamma), two of which are primary: alpha and beta.

Alpha cells

Alpha cells constitute 20% of the islet’s cells. They secrete the hormone glucagon, a polypeptide of 29 amino acids, which raises blood sugar to maintaiormal levels. For the most part, glucagon does not present the same problems as insulin and will not raise blood sugar much above normal — 80-100 mg of sugar per 100 ccs of blood. For obvious reasons (diabetes), we don’t want blood sugar to go too high. But for the brain, we don’t want it to go too low either (hypoglycemia). The brain does not store sugar and has no reserves. If blood sugar falls too low, the brain is affected in minutes, possibly even seconds. Note: all of the islet cells are serviced by an abundant network of capillaries that carry their “products,” including glucagon, out into the bloodstream.

The production and release of glucagon in the pancreas is regulated by chemoreceptors throughout the body that constantly measure the amount of sugar in the blood. Whenever blood sugar gets too low, the chemoreceptors signal the alpha cells in the pancreas to release more glucagon. Glucagon in turn travels through the bloodstream to the liver, where it acts on hepatocytes (cells in the liver) to break down glycogen (the stored form of glucose) into glucose through a process called glycogenolysis. Also, if required, the body can convert amino acids and/or fat into intermediate metabolites that are ultimately converted into glucose through a process called gluconeogenesis. In either case, the glucose makes its way into the bloodstream where it is available to be used by cells for energy.

Correspondingly, higher-than-normal blood sugar turns off the release of glucagon.

It should also be noted that stimulation of the sympathetic nervous system in preparation for stress, or flight (or in response to fright) also affects glucagon release; it increases it. This is accomplished through both neural and hormonal signals coming down into the pancreas. Hormonally, we’re talking about epinephrine and norepinephrine, which stimulate the release of glucagon, thus raising blood sugar levels.

And finally, glucagon secretion is inhibited by amylin, a peptide of 37 amino acids, which is secreted by the beta cells of the pancreas.
Injections of glucagon are sometimes given to diabetics suffering from an insulin reaction in order to speed the return of normal levels of blood sugar. All of glucagon’s actions tend to counter those of insulin, which works to reduce the level of glucose in the blood. Incidentally, glucagon, like insulin, is readily available thanks to genetically engineered bacteria and recombinant DNA technology. This is done by inserting the human gene for insulin into E. coli bacteria, which then “grow” genuine, bio-identical, human insulin in culture tanks. For those squeamish about E. coli, this process is also done by some manufacturers using yeast instead of bacteria.

Beta cells

Beta cells constitute approximately 80% of islet cells. They secrete insulin, which lowers blood sugar — also in response to chemoreceptors. Higher-than-normal blood sugar stimulates beta cells to release insulin. Sustained high blood sugar is bad not only for the blood but also for organs and cells.

Beta cells have channels in their plasma membrane that serve as glucose detectors. Beta cells secrete insulin in response to a rising level of circulating glucose (i.e. “blood sugar”).

Insulin is a small protein that affects virtually every single cell in the body and most organs — primarily by regulating how every cell in the body utilizes glucose. Seventy-five percent of that glucose is ultimately used by the body to sustain brain function. The remaining 25% is divided between muscle function, red blood cell production, and powering every single cell in the body. Actually, glucose does not power those cells directly, but rather, through a process known as glycolysis, it is used in the creation of pyruvate, which is then turned into adenosine triphosphate (ATP), the actual energy source within the cell.

Again, insulin is a primary regulator of sugar in the body. For example, it stimulates skeletal muscle fibers to take up glucose and convert it into glycogen, which is the storage form of glucose and is utilized in muscle tissue to produce ATP by the muscle itself. Insulin also works inside muscle tissue to extract amino acids from the blood and stimulate their conversion into protein, thereby causing the muscles to “grow.”

Insulin also acts on liver cells, stimulating them to take up glucose from the blood and convert it into glycogen while inhibiting production of the enzymes involved in breaking glycogen back down into glucose and inhibiting the conversion of fats and proteins into glucose. In this way, insulin helps regulate the body’s energy storage system. It should be noted that when the dietary intake of high glycemic carbohydrates is excessive, this leads to an excess of stored fat in the liver, which ultimately compromises liver function. This is further compounded by the fact that insulin acts on fat cells to stimulate their uptake of glucose and the synthesis of fat.

In each case, insulin triggers these effects by binding to the insulin receptor — a transmembrane protein embedded in the plasma membrane of the responding cells.

Taken together, all of these insulin actions result in the storage of the soluble nutrients absorbed from the intestine into insoluble, energy-rich products (glycogen, protein, fat) and a drop in the level of blood sugar. Specifically, insulin is glucagon’s opposite and acts on the cells of the body to:

· Increase the speed and ability of glucose to diffuse into cells — especially the skeletal muscles and heart muscles for the restoration and recovery of those muscles.

· Accelerate the conversion of glucose into its storage form, glycogen.

· Increase the synthesis of proteins from amino acids.

· Increase the synthesis of fatty acids — especially in the liver. This is the mechanism animals in the wild use to store energy for hibernation or just to survive harsh winters. Unfortunately, it causes problems for modern man as we no longer face such extreme conditions — thus leading to an excess of fat storage.

· It decreases the rate of glycogenolysis (breakdown of glycogen into glucose) and gluconeogenesis (conversion of fats and proteins into glucose). The net effect is to lower glucose levels.

Lower-than-normal blood glucose turns off the output of insulin. But there are other factors that also affect insulin release. The parasympathetic nervous system can stimulate insulin release to aid in recovery and rest. Glucagon itself causes insulin release to balance its effect in a negative feedback loop. And finally, gastric inhibitory peptide (GIP) from the enteroendocrine cells of the small intestine responds to glucose in the lumen of the gut, thereby signaling the “preparatory” release of glucose-dependent insulin from pancreatic beta cells. It should be noted that the effect of GIP on the pancreas is diminished by Type 2 diabetes.

And finally, beta cells also produce insulin-like growth factors (specifically, IGF-2), which is found in many body tissues at concentrations far higher than insulin itself. It shares the molecular structure and shape of insulin and is involved in growth. As a side note, IGF-1 (produced in the liver) and IGF-2 are used by cancer cells to stimulate growth.

Delta cells

Delta cells constitute less than 1% of pancreatic islets. They secrete somatostatin, the same growth-hormone-inhibiting hormone secreted by the hypothalamus. This hormone inhibits insulin release and slows absorption of nutrients from the GI tract.

Gamma cells (F cells)

Gamma cells also constitute less than 1% of pancreatic islets. They secrete a pancreatic polypeptide that inhibits the release of somatostatin. In other words, Delta cells and Gamma cells work to regulate each other.

Diabetes mellitus (“sweet urine”)

Diabetes mellitus is actually not one disease, but a group of disorders in which glucose levels are elevated in the blood. It is called a protean (widespread) disease because it affects every system in the body. (For more on this concept, check out Diabetes — The Echo Effect — highly recommended.) By itself, it ranks somewhere between fourth and sixth as a leading cause of death in the US — and climbing the charts throughout the rest of the world. But when considered as a major factor in cardiovascular disease and kidney failure, its true impact is probably much higher. Its name, sweet urine, comes from the fact that it was originally diagnosed by tasting (not testing) the patient’s urine. The word “mellitus” is Latin for honey-sweet. Elevated glucose levels make the urine sweet. Back then, doctors truly earned their fees.

Doctors often refer to the clinical manifestations of diabetes as the “three polys“:

· Polyuria: copious amounts of urine.

· Polydipsia: excessive thirst and drinking of water — caused by the polyuria.

· Polyphagia: excessive eating. Patients with diabetes are actually starving because they’re not getting sugar into their cells where it is needed — so they are driven to eat excessively, in an attempt to compensate.

There are two main types of diabetes. Type I is insulin-dependent diabetes mellitus and Type II is non-insulin-dependent diabetes, formerly known as maturity-onset or adult onset diabetes. There is also a third, less common, type of diabetes that results from mutant genes inherited from one or both parents. We will discuss all three types.

Type I represents about 10-20% of all diabetes cases. It is suspected that it is an autoimmune disease in which the body becomes allergic to its own beta cells and destroys them. What triggers this attack is still unknown, although a prior viral infection may be the culprit. In any case, the net result is that there are simply too few beta cells left to make enough insulin to fulfill the body’s needs, and the patient ends up with an absolute deficiency in the quantity of insulin available. Type I diabetes is also known as juvenile-onset diabetes because it often appears in childhood.

Standard “medical” treatment is daily insulin injections to give patients the insulin their bodies are not providing. Unfortunately, because insulin demands fluctuate so frequently during the day, it is very hard to regulate “external” insulin in a way that keeps sugar and insulin levels consistently balanced in the body. For example, injections after vigorous exercise or long after a meal may drive the blood sugar level down to a dangerously low value causing an insulin reaction. The patient becomes irritable, fatigued, and may lose consciousness. In response, doctors have developed experimental treatments such as inhalable insulin, pancreatic transplants, islet cell transplants, immune suppression, and insulin pumps. To this point, none of these alternatives is without significant problems. On the other hand, although it cannot be controlled with diet and exercise, there are indeed alternative options that can prove helpful. We’ll talk about those a little later.

In addition to the immediate problems associated with excess blood sugar, diabetes also presents other problems. For example, patients are in a chronic state of starvation, unable to use nutrients without injections of insulin. In addition, cataracts of the lens of the eye and diabetic retinopathy are related to high blood sugar. The excess sugar diffuses into the eye and forms a cloudy glycoprotein with the lens. Another problem associated with diabetes is if the body is unable to utilize blood sugar as energy for the cells of the body, it will try and convert as much of the excess glucose as possible into fat to store the energy. This not only leads to fatty livers, but to an excess of fat in the blood. High levels of fat in the blood, over long periods, leads to atherosclerosis. Other physical problems related to high blood lipids and blood vessel damage (also caused by blood sugar) include strokes, heart attacks, kidney failure, peripheral vascular disease, and increased rates of infection — not to mention, a high rate of amputation. (Again, check out Diabetes — The Echo Effect.)

There is another problem associated with Type I diabetes. Since diabetics cannot use glucose for energy effectively, their bodies shift to using fatty acids to produce cellular energy. This results in an excess of fatty acid wastes called ketones. Ketones are very, very acidic, and they cause a shift to acidity in the blood. This condition is called ketoacidosis. You can smell acetone on the breath of a diabetic suffering from ketoacidosis. Uncorrected, ketoacidosis is rapidly fatal.

It’s probably worth mentioning that low-carb diets work by turning dieters into “controlled” diabetics so that their bodies can shift from sugar burning to fat burning. Effectively, low-carb diets interrupt the Krebs cycle by denying the body the 100 grams of glucose it needs to prime the pump for sugar burning. As I mentioned, this process essentially turns dieters into controlled low-level diabetics and produces a mild form of ketoacidosis. As a side note, if a dieter eats protein and fat, then triggers the Krebs cycle, all excess material will be turned into fat anyway — so ultimately, little is gained unless one chooses to remain permanently a low level diabetic.

For more on low-carb diets, check out my series of newsletters on the subject, Low Carb Craziness.

At one time, Type II diabetes was known as adult onset diabetes because almost all its victims tended to be over 40 years of age. But those days are long gone, and now, thanks to catastrophic dietary changes in the developed world (and with developing countries struggling to imitate us) Type II diabetes is now appearing in many children. So it has been renamed. It is now called non-insulin-dependent diabetes and accounts for some 90% of all diabetes cases. In fact, childreow account for 20% of all newly-diagnosed cases of Type II diabetes and, like their adult counterparts, are usually overweight. Sadly, it is almost always a self-inflicted disease — most often triggered by high glycemic diets and excessive weight. Fortunately, because it is self-inflicted, it is usually much milder than Type I diabetes (at least if caught in the early stages) and is much easier to control. In fact, many patients have normal insulin levels. The problem is that because the body has had to pump out so much insulin over time to combat the high glycemic foods dominating so many diets, the cells of the body have become progressively less sensitive to the action of insulin. They have, to use the common term, become insulin resistant.

Although virtually every single cell in the body survives by converting glucose to energy, skeletal muscle is the major “sink” for removing excess glucose from the blood and converting it into glycogen). But in a Type II diabetic, the ability of skeletal muscle to remove glucose from the blood and convert it into glycogen may be only 20% of normal. This, again, is called insulin resistance. Fortunately, vigorous exercise increases the ability of skeletal muscle to transport glucose across its cellular membrane, thus reducing the effect of insulin resistance. Or to put it another way, people who lead sedentary lives are more likely to develop Type II diabetes.

Symptoms of Type II diabetes are similar to that found in Type I and include the three polys mentioned above.

Treatment options include:

· For most patients — diet, weight loss, and exercise.

· For some patients — pharmaceutical drugs.

· For a few patients — insulin injections.

On the other hand, if patients are lax and do not control their disease early on, symptoms become more severe over time. It is as though after years of pumping out insulin in an effort to overcome the patient’s insulin resistance, the beta cells become exhausted.

Note: there is a close relative of Type II diabetes called gestational diabetes. It usually results from transient elevations in blood glucose during pregnancy. It causes the same problems as Type II diabetes for the fetus.

Inherited Forms of Diabetes Mellitus

A very small number of cases of diabetes result from mutant genes inherited from one or both parents. These genes can cause diabetes in several different ways.

· Some mutant genes prevent the body from actually manufacturing insulin.

· Other genes cause insulin receptor sites on cells to malfunction.

· Still another mutation prevents the body from manufacturing glucokinase, an enzyme essential for glycolysis, the first step in converting glucose into ATP, which energizes every single cell in the body.

· And yet another mutation messes up the sodium-potassium pump mechanism (used to transport large molecules into and out of cells) in the beta cells of the pancreas so that the insulin they create caever leave the cell and make its way into the bloodstream. In other words, the insulin is there, but unusable.

While the symptoms of inherited diabetes usually appear in childhood or adolescence, patients with inherited diabetes differ from most children with Type 2 diabetes in that their families have a history of similar problems and they are not necessarily obese. But again, inherited diabetes represents only a small percentage of diabetic patients.

Gonads

The gonads—ovaries in females and testes in males—are responsible for producing the sex hormones of the body. These sex hormones determine the secondary sex characteristics of adult females and adult males.

· Testes: The testes are a pair of ellipsoid organs found in the scrotum of males that produce the androgen testosterone in males after the start of puberty. Testosterone has effects on many parts of the body, including the muscles, bones, sex organs, and hair follicles. This hormone causes growth and increases in strength of the bones and muscles, including the accelerated growth of long bones during adolescence. During puberty, testosterone controls the growth and development of the sex organs and body hair of males, including pubic, chest, and facial hair. In men who have inherited genes for baldness testosterone triggers the onset of androgenic alopecia, commonly known as male pattern baldness.

· Ovaries: The ovaries are a pair of almond-shaped glands located in the pelvic body cavity lateral and superior to the uterus in females. The ovaries produce the female sex hormones progesterone and estrogens. Progesterone is most active in females during ovulation and pregnancy where it maintains appropriate conditions in the human body to support a developing fetus. Estrogens are a group of related hormones that function as the primary female sex hormones. The release of estrogen during puberty triggers the development of female secondary sex characteristics such as uterine development, breast development, and the growth of pubic hair. Estrogen also triggers the increased growth of bones during adolescence that lead to adult height and proportions.

Thymus

The thymus is a soft, triangular-shaped organ found in the chest posterior to the sternum. The thymus produces hormones called thymosins that help to train and develop T-lymphocytes during fetal development and childhood. The T-lymphocytes produced in the thymus go on to protect the body from pathogens throughout a person’s entire life. The thymus becomes inactive during puberty and is slowly replaced by adipose tissue throughout a person’s life.

Other Hormone Producing Organs

In addition to the glands of the endocrine system, many other non-glandular organs and tissues in the body produce hormones as well.

· Heart: The cardiac muscle tissue of the heart is capable of producing the hormone atrial natriuretic peptide (ANP) in response to high blood pressure levels. ANP works to reduce blood pressure by triggering vasodilation to provide more space for the blood to travel through. ANP also reduces blood volume and pressure by causing water and salt to be excreted out of the blood by the kidneys.

· Kidneys: The kidneys produce the hormone erythropoietin (EPO) in response to low levels of oxygen in the blood. EPO released by the kidneys travels to the red bone marrow where it stimulates an increased production of red blood cells. The number of red blood cells increases the oxygen carrying capacity of the blood, eventually ending the production of EPO.

· Digestive System: The hormones cholecystokinin (CCK), secretin, and gastrin are all produced by the organs of the gastrointestinal tract. CCK, secretin, and gastrin all help to regulate the secretion of pancreatic juice, bile, and gastric juice in response to the presence of food in the stomach. CCK is also instrumental in the sensation of satiety or “fullness” after eating a meal.

· Adipose: Adipose tissue produces the hormone leptin that is involved in the management of appetite and energy usage by the body. Leptin is produced at levels relative to the amount of adipose tissue in the body, allowing the brain to monitor the body’s energy storage condition. When the body contains a sufficient level of adipose for energy storage, the level of leptin in the blood tells the brain that the body is not starving and may work normally. If the level of adipose or leptin decreases below a certain threshold, the body enters starvation mode and attempts to conserve energy through increased hunger and food intake and decreased energy usage. Adipose tissue also produces very low levels of estrogens in both men and women. In obese people the large volume of adipose tissue may lead to abnormal estrogen levels.

· Placenta: In pregnant women, the placenta produces several hormones that help to maintain pregnancy. Progesterone is produced to relax the uterus, protect the fetus from the mother’s immune system, and prevent premature delivery of the fetus. Human chorionic gonadotropin (HCG) assists progesterone by signaling the ovaries to maintain the production of estrogen and progesterone throughout pregnancy.

· Local Hormones: Prostaglandins and leukotrienes are produced by every tissue in the body (except for blood tissue) in response to damaging stimuli. These two hormones mainly affect the cells that are local to the source of damage, leaving the rest of the body free to functioormally.

1. Prostaglandins cause swelling, inflammation, increased pain sensitivity, and increased local body temperature to help block damaged regions of the body from infection or further damage. They act as the body’s natural bandages to keep pathogens out and swell around damaged joints like a natural cast to limit movement.

2. Leukotrienes help the body heal after prostaglandins have taken effect by reducing inflammation while helping white blood cells to move into the region to clean up pathogens and damaged tissues.

Physiology of the Endocrine System

Endocrine System vs. Nervous System Function

The endocrine system works alongside of the nervous system to form the control systems of the body. The nervous system provides a very fast and narrowly targeted system to turn on specific glands and muscles throughout the body. The endocrine system, on the other hand, is much slower acting, but has very widespread, long lasting, and powerful effects. Hormones are distributed by glands through the bloodstream to the entire body, affecting any cell with a receptor for a particular hormone. Most hormones affect cells in several organs or throughout the entire body, leading to many diverse and powerful responses.

Hormone Properties

Once hormones have been produced by glands, they are distributed through the body via the bloodstream. As hormones travel through the body, they pass through cells or along the plasma membranes of cells until they encounter a receptor for that particular hormone. Hormones can only affect target cells that have the appropriate receptors. This property of hormones is known as specificity. Hormone specificity explains how each hormone can have specific effects in widespread parts of the body.

Many hormones produced by the endocrine system are classified as tropic hormones. A tropic hormone is a hormone that is able to trigger the release of another hormone in another gland. Tropic hormones provide a pathway of control for hormone production as well as a way for glands to be controlled in distant regions of the body. Many of the hormones produced by the pituitary gland, such as TSH, ACTH, and FSH are tropic hormones.

Hormonal Regulation

The levels of hormones in the body can be regulated by several factors. The nervous system can control hormone levels through the action of the hypothalamus and its releasing and inhibiting hormones. For example, TRH produced by the hypothalamus stimulates the anterior pituitary to produce TSH. Tropic hormones provide another level of control for the release of hormones. For example, TSH is a tropic hormone that stimulates the thyroid gland to produce T3 and T4. Nutrition can also control the levels of hormones in the body. For example, the thyroid hormones T3 and T4 require 3 or 4 iodine atoms, respectively, to be produced. In people lacking iodine in their diet, they will fail to produce sufficient levels of thyroid hormones to maintain a healthy metabolic rate. Finally, the number of receptors present in cells can be varied by cells in response to hormones. Cells that are exposed to high levels of hormones for extended periods of time can begin to reduce the number of receptors that they produce, leading to reduced hormonal control of the cell.

Classes of Hormones

Hormones are classified into 2 categories depending on their chemical make-up and solubility: water-soluble and lipid-soluble hormones. Each of these classes of hormones has specific mechanisms for their function that dictate how they affect their target cells.

· Water-soluble hormones: Water-soluble hormones include the peptide and amino-acid hormones such as insulin, epinephrine, HGH, and oxytocin. As their name indicates, these hormones are soluble in water. Water-soluble hormones are unable to pass through the phospholipid bilayer of the plasma membrane and are therefore dependent upon receptor molecules on the surface of cells. When a water-soluble hormone binds to a receptor molecule on the surface of a cell, it triggers a reaction inside of the cell. This reaction may change a factor inside of the cell such as the permeability of the membrane or the activation of another molecule. A common reaction is to cause molecules of cyclic adenosine monophosphate (cAMP) to be synthesized from adenosine triphosphate (ATP) present in the cell. cAMP acts as a second messenger within the cell where it binds to a second receptor to change the function of the cell’s physiology.

· Lipid-soluble hormones: Lipid-soluble hormones include the steroid hormones such as testosterone, estrogens, glucocorticoids, and mineralocorticoids. Because they are soluble in lipids, these hormones are able to pass directly through the phospholipid bilayer of the plasma membrane and bind directly to receptors inside the cell nucleus. Lipid-soluble hormones are able to directly control the function of a cell from these receptors, often triggering the transcription of particular genes in the DNA to produce “messenger RNAs (mRNAs)” that are used to make proteins that affect the cell’s growth and function.

Every reaction in your body, from breaking down food into energy, the mood swings that you have, physiological development of your body, development of your reproductive system, etc. are all carried out by certain chemicals. These certain chemicals are known as hormones in your body. These slow processes that take time to develop are a part of the endocrine system functions. Breathing, body movement, sudden reaction to the surroundings are a part of the nervous system functions.

The endocrine systems consists of hormones and glands. Hormones are the chemical messengers of the body that travel down to the various body parts concerned transferring information. There are many hormones secreted by the endocrine organs, and each individual hormone affects only those body cells that have a genetic program that allows them to react only to those hormones that are related to them. The hormones influence the body to react according to the changes in the balance of fluids and minerals in blood, stress, infection, etc.

The hormones secreted by the endocrine organs are very important for regulating metabolic processes, growth of the body and sexual development. These glands release the hormones into the blood stream and are transported to the various cells and body parts. When the hormones reach the target site, they bind to the receptor cells with a lock and key mechanism. The hormone may be present within the nucleus or on the surface of the cells. Once bound to the receptor, the hormones transmit a signal that triggers an action by the site. Hormones control the organ’s function and affect the growth and development of the organs. It is due to the hormones that the sexual characteristics of the organs develop and act accordingly. They also determine the use and storage of energy in the body, regulate the fluid, salt and sugar levels in the blood. Minute amount of hormones trigger large reactions within the body. All hormones are proteins, but all proteins are not hormones. Steroids are not derived from proteins, but from the fatty substances from cholesterol.

The body has a well-controlled feedback system that manages the on/off button of the endocrine gland. When the chemical level or the nutrient level in the body is abnormally high or low, the endocrine glands secrete hormones. Once the level of the body fluids is normal the hormones secretions is shut down. When the glands receive information to secrete hormones, it is a positive feedback mechanism. If the glands receives information to stop the secretions of the hormones, it is known as negative feedback.

Functions of Endocrine System

The endocrine system is a collection of glands that secrete different hormones for the various functions and chemical reactions occurring within the body. The main function is to maintain a stable environment within the body or homeostasis. For example, maintaining the blood sugar levels according to changes occurring in the body is homeostasis. The other function of is promoting the structural changes of the body. For example, the permanent changes occurring in the body over time like height, development of sexual organs, etc. is a part of the structural changes.

There are 8 major glands that help in the functioning of this vital system. These major endocrine glands are as follows:

Hypothalamus

Pituitary gland

Parathyroid gland

Thyroid gland

Adrenal glands

Pancreas

Ovaries (in female body)

Testes (in male body)

Let us know more about the various functions with the help of the above mentioned endocrine glands.

Hypothalamus: A collection of specialized cells that are located in the lower central part of the brain is called the hypothalamus. The hypothalamus is the main link between the endocrine and the nervous systems. The nerve cells of the hypothalamus control the pituitary gland by stimulating or suppressing the hormone secretions.

Pituitary Gland: The pituitary gland is located at the base of the brain just below the hypothalamus. The pituitary gland is the most important part in the endocrine system. The pituitary gland secretes hormones on the basis of the emotional and seasonal changes. The hypothalamus sends information that is sensed by the brain to pituitary triggering production hormones. The pituitary gland is divided into two parts: the anterior lobe and the posterior lobe. The anterior lobe of the pituitary gland regulated the activity of the thyroid, adrenals, and the reproductive glands. The anterior lobe also produces hormones like:

Growth Hormone: To stimulate the growth of the bones and tissues. It also plays a role in the body’s absorption of nutrients and minerals.

Prolactin: To activate the production of milk in lactating mothers

Thyrotropin: To stimulate the thyroid gland to produce thyroid hormones

Corticotropin: To stimulate the adrenal glands to produce certain hormones.

Endorphins are also secreted by the pituitary that acts on the nervous system and reduces the feeling of pain. The pituitary glands produces hormones that signal the reproductive organs to secrete sex hormones. The menstrual cycle and ovulation in women is also controlled by the pituitary gland. The posterior lobe of the pituitary gland produces antidiuretic hormone that helps to control the water balance in the body. Oxytoxins that trigger the contractions of the uterus in a woman who is in labor is secreted by the posterior lobe.

Thyroid Gland: The thyroid gland is situated in the front part of the lower neck that is shaped like a bow tie or butterfly. The production and secretions of the hormones of the thyroid glands are controlled by thyrotropin secreted by the pituitary gland. Thyroid produces thyroxine and triiodothyronine, that controls the rate at which the cells use up energy from food for production of energy. The thyroid hormones are very important as they help in growth of bones and the development and growth of the brain and nervous system in children. Over or under secretion of thyroid hormones leads to a number of thyroid problems in the body.

Parathyroids: These are four tiny glands that are attached to the thyroid gland. They release the parathyroid hormone that helps in regulating the level of calcium in blood along with another hormone produced by thyroid known as calcitinin.

Adrenal Glands: On each of the two kidneys, there are two triangular adrenal glands situated. The adrenal gland is divided into two parts. The outer part called the adrenal cortex produces corticosteroids, that influence and regulate the salt and water levels. They are also helpful in the body’s response to stress, metabolism, immune system and the function and development of sexual organs. The inner part called the adrenal medulla, secretes catecholamines like epinephrine. This hormone is also called the adrenaline, it increases the blood pressure and heart rate when the body is under stress.

Reproductive Glands or Gonads: The gonads are present in males and females and are the main organs producing sex hormones. In men, the gonads are related to testes. The testes are located in the scrotum and secrete androgens. The most important hormone for men testosterone is secreted from the testes. In women, ovaries are the gonads that are located in the pelvis region. They produce estrogen and progesterone hormones. Estrogen is involved during the sexual maturation of the girl, that is, puberty. Progesterone along with estrogen is involved in the regulation of menstruation cycle. These hormones are also involved during pregnancy.

Pancreas: These glands are associated with the digestive system of the human body. They secrete digestive enzymes and two important hormones insulin and glucagon. These hormones work together to maintain the level of glucose in the blood. If these hormones are not secreted in the required levels, it leads to development of diabetes.

Pineal: The pineal gland is located in the center of the brain. Melatonin is secreted by this gland that helps regulate the sleeping cycle of a person.

How Does Endocrine System Function with Other Systems?

The system that helps the body communicate, control and coordinate various functions is the endocrine system. The other systems with which this system interacts includes the nervous system, the reproductive system, liver, gut, pancreas, fat and the kidneys. This interaction is carried out via a network of glands and organs. These glands and organs can produce, store and secrete many types of hormones. Thus, this system helps control and regulate:

Reproductive system: Helps in controlling the formation of gametes

Skeletal system: Helps in controlling the growth of bones

Muscular system: Helps in controlling muscle metabolism

Excretory system: Helps control water in the kidneys

Respiration system: Helps in controlling the rate of respiration

The interaction with these systems helps in maintaining the energy levels within the body. It also affects the growth and development of the body as well as maintaining homeostasis. When one or more than one of the organs stop functioning or function abnormally, it leads to diseases and disorders. It leads to over or under production of hormones, that causes hormonal imbalance. The imbalance sends the normal functioning of other systems and organs to a toss, leading to diseases and disorders. For example, when the pancreas as affected it leads to diabetes.

The hypothalamus oversees many internal body conditions. It receives nervous stimuli from receptors throughout the body and monitors chemical and physical characteristics of the blood, including temperature, blood pressure, and nutrient, hormone, and water content. When deviations from homeostasis occur or when certain developmental changes are required, the hypothalamus stimulates cellular activity in various parts of the body by directing the release of hormones from the anterior and posterior pituitary glands. The hypothalamus communicates directives to these glands by one of the following two pathways:

· Communication between the hypothalamus and the anterior pituitary occurs through chemicals (releasing hormones and inhibiting hormones) that are produced by the hypothalamus and delivered to the anterior pituitary through blood vessels. The releasing and inhibiting hormones are produced by specialized neurons of the hypothalamus called neurosecretory cells. The hormones are released into a capillary network (primary plexus) and transported through veins (hypophyseal portal veins) to a second capillary network (secondary plexus) that supplies the anterior pituitary. The hormones then diffuse from the secondary plexus into the anterior pituitary, where they initiate the production of specific hormones by the anterior pituitary. The releasing and inhibiting hormones secreted by the hypothalamus and the hormones produced in response by the anterior pituitary are listed in Table 1 . Many of the hormones produced by the anterior pituitary are tropic hormones (tropins), hormones that stimulate other endocrine glands to secrete their hormones.

TABLE 1

Hormone Functions

Source

Hormone (H), Releasing Hormone (RH), Or Inhibiting Hormone (IH)

Chemical Form*

Target

Action

Hypothalamus

GHRH

growth hormone RH

anterior pituitary

inhibits release of hGH

GHIH

growth hormone IH (somatostatin)

anterior pituitary

stimulates release of hGH

TRH

thyrotropin RH

anterior pituitary

stimulates release of TSH and hGH

GnRH

gonadotropin RH

anterior pituitary

stimulates release of LH and FSH

PRH

prolactin RH

anterior pituitary

stimulates release of PRL

PIH

prolactin IH (dopanmine)

anterior pituitary

inhibits release of PRL

CRH

corticotropin RH

anterior pituitary

stimulates release of ACTH

Anterior pituitary (tropic hormones)

TSH

thyroid stimulating H (thyrotropin)

thyroid

stimulates secretion of T₃ and T₄

ACTH

adrenocortico-tropic hormone

adrenal cortex

stimulates secretion of glucocorticoids

FSH

follicle-stimulating hormone

ovary, testes

regulates oogenesis & spermatogenesis

luteinizing hormone

ovary, testes

regulates oogenesis & spermatogenesis

Anterior pituitary (hormones)

PRL

prolactin

mammary glands

stimulates production of milk

hGH

human growth H (somatotropin)

bone, muscle, various

stimulates growth

Posterior pituitary

oxytocin

uterus, mammary glands

uterine contractions, release of milk

ADH

antidiuretic H (vasopressin)

kidneys, sweat glands

increases water retention

Thyroid gland

T₄

thyroxine

most body cells

increases rate of cellular metabolism

T₃

triiodothyronine

bone

increases rate of cellular metabolism

calcitonin

bone

decreases blood Ca²⁺

Parathyroid gland

PTH

parathyroid hormone

bone, kidneys, intestine

increases blood Ca²⁺

Adrenal medulla

epinephrine (adrenaline)

blood vessels, liver, heart

increases blood sugar, constricts blood vessels (fight-or-flight response)

norepinephrine (noradrenaline)

blood vessels, liver, heart

increases blood sugar constricts blood vessels (fight or flight response)

Adrenal cortex

mineralocorticoids (e.g., aldosterone)

kidneys

increase reabsorption of Na⁺, excretion of K⁺

glucocorticoids (e.g., cortisol)

most body cells

increase blood sugar

androgens (e.g., DHEA)

general

stimulate onset of puberty, female sex drive

Pancreas

glucagon (secreted by alpha cells)

liver

increases blood glucose

insulin (secreted by beta cells)

liver, muscle, adipose

decreases blood glucose

somatostatin (secreted by delta cells)

alpha & beta cells

inhibits insulin & glucagon release

pancreatic polypeptide (from F cells)

delta cells

inhibits somato-statin & pancreatic enzymes

Ovaries

estrogen

uterus, general

menstrual cycle, secondary sex characteristics

progesterone

uterus

regulates menstrual cycle, pregnancy

relaxin

pelvis, cervix

dilates cervix & birth canal

inhibin

anterior pituitary

inhibits FSH release

Testes

testosterone

testes, general

spermatogenesis, secondary sex characteristics

inhibin

anterior pituitary

inhibits FSH release

Pineal

melatonin

various

regulates biological clock

Kidney

erythropoietin

bone marrow

increases blood cell production

calcitriol (Vitamin d)

intestine

increases Ca²⁺ absorption

Placenta

estrogen

uterus

maintains pregnancy, mammary glands

progesterone

uterus

maintains pregnancy, mammary glands

hCG

ovary

stimulates release of estrogen & progesterone

hCS

mammary glands

prepares mammary glands for lactation

Gastrointestinal tract

gastrin

stomach

stimulates HCI release

GIP

gastrin inhibitory peptide

stomach, pancreas

inhibits gastric juice release, increases insulin

secretin

pancreas, liver

stimulates release of enzymes & bile

CCK

cholecystokinin

pancreas, liver

stimulates release of enzymes & bile

serotonin

stomach

stimulates stomach muscle contraction

Heart

ANP

atrial natriuretic peptide

kidney, adrenal cortex

decreases blood pressure

Most cells

prostaglandins

all cells except red blood cells

various

leukotrienes

all cells except red blood cells

various

· Communication between the hypothalamus and the posterior pituitary occurs through neurosecretory cells that span the short distance between the hypothalamus and the posterior pituitary. Hormones produced by the cell bodies of the neurosecretory cells are packaged in vesicles and transported through the axon and stored in the axon terminals that lie in the posterior pituitary. When the neurosecretory cells are stimulated, the action potential generated triggers the release of the stored hormones from the axon terminals to a capillary network within the posterior pituitary. Two hormones, oxytocin and antidiuretic hormone (ADH), are produced and released in this way. Their functions are summarized in Table 1 .

Anterior Pituitary Hormones.

(1) Growth hormone: causes growth of almost all cells and tissues of the body.

(2) Adrenocorticotropin: causes the adrenal cortex to secrete adrenocortical hormones.

(3) Thyroid-stimulating hormone: causes the thyroid gland to secrete thyroxine and triiodothyronine.

(4) Follicle-stimulating hormone: causes growth of follicles in the ovaries prior to ovulation, promotes the formation of sperm in the testes.

(5) Luteinizing hormone: plays an important role in causing ovulation; also causes secretion of female sex hormones by the ovaries and testosterone by the testes.

(6) Prolactin: promotes development of the breasts and secretion of milk. Posterior Pituitary Hormones.

(1) Antidiuretic hormone (also called vasopressin): causes the kidneys to retain water, thus increasing the water content of the body; also, in high concentrations, causes constriction of the blood vessels throughout the body and elevates the blood pressure.

(2) Oxytocin: contracts the uterus during the birthing process, thus perhaps helping expel the baby; also contracts myoepithelial cells in the breasts, thereby expressing milk from the breasts when the baby suckles.

Adrenal Cortex.

(1) Cortisol: have multiple metabolic functions for control of the metabolism of proteins, carbohydrates, and fats.

(2) Aldosterone: reduces sodium excretion by the kidneys and increases potassium excretion, thus increasing sodium in the body while decreasing the amount of potassium.

From this overview of the endocrine system, it is clear that most of the metabolic functions of the body are controlled one way or another by the endocrine glands. For instance, without growth hormone, the person remains a dwarf. Without thyroxine and triidothyronine from the thyroid gland, almost all the chemical reactions of the body become sluggish, and the person becomessluggish as well. Without insulin from the pancreas, the body’s cells can utilize very little of the food carbohydrates for energy. And, without the sex hormones, sexual development and sexual functions are absent.

CHEMISTRY OF THE HORMONES

Chemically, the hormones are of three basic types:

(1) Steroid hormones: These all have a chemical structure similar to that of cholesterol and in most instances are derived from cholesterol itself. Different steroid hormones are secreted by

(a) the adrenal cortex (cortisol and aldosterone),

(b) the ovaries (estrogen and progesterone), (c) the testes (testosterone), and (d) the placenta (estrogen and progesterone),

(2) Derivatives of the amino acid tyrosine: Two groups of hormones are derivatives of the amino acid tyrosine. The two metabolic thyroid hormones, thyroxine and triiodothyromine, are iodinated forms of tyrosine derivatives. And the two principal hormones of the adrenal medullae, epinephrine and norepinephrine, are both catecholamines, also derived from tyrosine.

(3) Proteins or peptides: All the remaining important endocrine hormones are either proteins, peptides, or immediate derivatives of these. The anterior pituitary hormones are either proteins or large polypeptides; the posterior pituitary hormones, antidiuretic hormone and oxytocin, are peptides containing only eight amino acids. And insulin, glucagon, and parathormone are all large polypeptides.

HORMONE RECEPTORS AND THEIR ACTIVATION

The endocrine hormones almost never act directly on the intracellular machinery to control the different cellular chemical reactions; instead, they almost invariably first combine with hormone receptors on the surfaces of the cells or inside the cells. The combination of hormone and receptor then usually initiates a cascade of reactions in the cell.

Either all or almost all hormonal receptors are very large proteins, and each cell usually has some 2000 to 10,000 receptors.

Also, each receptor is usually highly specific for a single hormone; this determines the type of hormone that will act on a particular tissue. Obviously, the target tissues that are affected by a hormone are those that contain its specific receptors.

The locations of the receptors for the different types of hormones are generally the following:

(1) In the membrane. The membrane receptors are specific mostly to the protein, peptide, and catecholamine (epinephrine and norepinephrine) hormones.

(2) In the cytoplasm. The receptors for the different steroid hormones are found almost entirely in the cytoplasm.

(3) In the nucleus. The receptors for the metabolic thyroid hormones (thyroxine and triiodothyronine) are found in the nucleus, believed to be located in direct association with one or more of the chromosomes.

Pharmacology

MECHANISMS OF HORMONAL ACTION

Activation of the Receptors. The receptors in their unbound state usually are inactive, and the intracellular mechanisms that are associated with them are also inactive. However, in a few instances the unbound receptors are in the active form, and when bound with the hormone they become inhibited.

Activation of a receptor occurs in different ways for different types of receptors.

In general, the transmitter substance combines with the receptor and causes a conformational change of the receptor molecule; this in turn alters the membrane permeability to one or more ions, especially sodium, chloride, potassium, and calcium ions. A few of the general endocrine hormones also function in this same way – for instance, the effect of epinephrine and norepinephrine in changing the membrane permeability in certain of their target tissues.

In addition to this occasional direct effect of hormone receptors to change cell membrane permeability, there are also two very important general mechanisms by which a large share of the hormones function: (1) by activating the cyclic AMP system of the cells, which in turn activates multiple other intracellular functions; or (2) by activating the genes of the cell, which cause the formation of intracellular proteins that in turn initiate specific cellular functions. These two general mechanisms are described as follows:

THE CYCLIC AMP MECHANISM FOR CONTROLLING CELL FUNCTION – A “SECOND MESSENGER” FOR HORMONE MEDIATION

Many hormones exert their effects on cells by first causing the substance cyclic 3’, 5’-adenosine monophosphate (cyclic AMP) to be formed in the cell. Once formed, the cyclic AMP causes the hormonal effects inside the cell. Thus, cyclic AMP is an intracellular hormonal mediator. It is also frequently called a second messenger for hormone mediation—the “first messenger” being the original stimulating hormone.

The cyclic AMP mechanism has been shown to be a way in which all the following hormones (and many more) can stimulate their target tissues:

1. Adrenocorticotropin

2. Thyroid-stimulating hormone

Thyroxine, T₄

Triiodothyronine, T₃

The thyroid hormones, thyroxine (T₄) and triiodothyronine (T₃), are tyrosine-based hormones produced by the thyroid gland. An important component in the synthesis is iodine. The major form of thyroid hormone in the blood is thyroxine (T₄). The ratio of T₄ to T₃ released in the blood is roughly 20 to 1. Thyroxine is converted to the active T₃ (three to four times more potent than T₄) within cells by deiodinases (5′-iodinase). These are further processed by decarboxylation and deiodination to produce iodothyronamine (T₁a) and thyronamine (T₀a).

3. Luteinizing hormone

4. Follicle-stimulating hormone

5. Vasopressin

6. Parathyroid hormone

7. Glucagon

8. Catecholamines

9. Secretin

The hypothalamic releasing hormones.

The stimulating hormone first binds with a specific “receptor” for that hormone on the membrane surface of the target cell. The specificity of the receptor determines which hormone will affect the target cell. After binding with the membrane receptor, the combination of hormone and receptor activates the protein enzyme adenyl cyclase. This enzyme is also located in the membrane and is either bound directly with the receptor protein or closely associated with it. However, a large portion of the adenyl cyclase enzyme protrudes through the inner surface of the membrane into the cytoplasm and, when activated, causes immediate conversion of much of the cytoplasmic ATP into cyclic AMP.

Once cyclic AMP is formed inside the cell it activates still other enzymes. In fact, it usually activates a cascade of enzymes. That is, a first enzyme is activated and this activates another enzyme, which activates still a third, and so forth. The importance of this mechanism is that only a few molecules of activated adenyl cyclase in the cell membrane can cause many more molecules of the next enzyme to be activated, which can cause still many times that many molecules of the third enzyme to be activated, and so forth. In this way, even the slightest amount of hormone acting on the cell surface can initiate a very powerful cascading activating force for the entire cell.

The specific action that occurs in response to cyclic AMP in each type of target cell depends upon the nature of the intracellular machinery, some cells having one set of enzymes and other cells having other enzymes. Therefore, different functions are elicited in different target cells— such functions as

(1) initiating synthesis of specific intracellular chemicals,

(2) causing muscle contraction or relaxation,

(3) initiating secretion by the cells,

(4) altering the cell permeability,

(5) and many other possible effects.

ACTION OF STEROID HORMONES ON THE GENES TO CAUSE PROTEIN SYNTHESIS

A second major means by which hormones— specifically the steroid hormones secreted by the adrenal cortex, the ovaries, and the testes—act is to cause synthesis of proteins in the target cells; these proteins then function as enzymes or transport proteins that in turn activate other functions of the cells.

The sequence of events in steroid function is the following:

1. The steroid hormone enters the cytoplasm of the cell, where it binds with a specific receptor protein,

2. The combined receptor protein/hormone then diffuses into or is transported into the nucleus.

3. The combinatioow activates the transcription process of specific genes to form messenger RNA.

4. The messenger RNA diffuses into the cytoplasm where it promotes the translation process at the ribosomes to form new proteins.

To give an example, aldosterone, one of the hormones secreted by the adrenal cortex, enters the cytoplasm of renal tubular cells, which contain its specific receptor protein. Therefore, in these cells the above sequence of events ensues. After about 45 minutes, proteins begin to appear in the renal tubular cells that promote sodium reabsorption from the tubules and potassium secretion into the tubules. Thus, there is a characteristic delay in the beginning action of the steroid hormone of 45 minutes and up to several hours or even days for full action, which is in marked contrast to the almost instantaneous action of some of the peptide and amino acid-derived hormones, such as vasopressin and norepinephrine.

CONTROL OF PITUITARY SECRETION BY THE HYPOTHALAMUS

Almost all secretion by the pituitary is controlled by either hormonal or nervous signals from the hypothalamus. Indeed, when the pituitary gland is removed from its normal position beneath the hypothalamus and transplanted to some other part of the body, its rates of secretion of the different hormones (except for prolactin) fall to low levels – in the case of some of the hormones, almost to zero.

Secretion from the posterior pituitary is controlled by nerve fibers originating in the hypothalamus and terminating in the posterior pituitary. In contrast, secretion by the anterior pituitary is controlled by hormones called hypothalamic releasing and inhibitory hormones (or factors) secreted within the hypothalamus itself and then conducted to the anterior pituitary through minute blood vessels called hypothalamic-hypophysial portal vessels. In the anterior pituitary these releasing and inhibitory hormones act on the glandular cells to control their secretion.

Brain: Hypothalamus

Hypothalamic nuclei

The hypothalamus receives signals from almost all possible sources in the nervous system. Thus, when a person is exposed to pain, a portion of the pain signal is transmitted into the hypothalamus. Likewise, when a person experiences some powerful depressing or exciting thought, a portion of the signal is transmitted into the hypothalamus. Olfactory stimuli denoting pleasant or unpleasant smells transmit strong signal components directly and through the amygdaloid nuclei into the hypothalamus. Even the concentrations of nutrients, electrolytes, water, and various hormones in the blood excite or inhibit various portions of the hypothalamus. Thus, the hypothalamus is a collecting center for information concerned with the internal well-being of the body, and in turn much of this information is used to control secretions of the many globally important pituitary hormones.

THE HYPOTHALAMIC-HYPOPHYSIAL PORTAL SYSTEM

The anterior pituitary is a highly vascular gland with extensive capillary sinuses among the glandular cells. Almost all the blood that enters these sinuses passes first through a capillary bed in the tissue of the lower tip of the hypothalamus and then through sma:ll hypothalamic-hypophysial portal vessels into the anterior pituitary sinuses. Small blood vessels project into the substance of the median eminence and then return to its surface, coalescing to form the hypothalamic-hypophysial portal vessels. These in turn pass downward along the pituitary stalk to supply blood to the anterior pituitary sinuses.

Secretion of Hypothalamic Releasing and Inhibitory Hormones into the Median Eminence. Special neurons in the hypothalamus synthesize and secrete hormones called hypothalamic releasing and inhibitory hormones (or releasing and inhibitory factors) that control the secretion of the anterior pituitary hormones. These neurons originate in various parts of the hypothalamus and send their nerve fibers into the median eminence and the tuber cinereum, the hypothalamic tissue that extends into the pituitary stalk. The endings of these fibers are different from most endings in the central nervous system in that their function is not to transmit signals from one neuron to another but merely to secrete the hypothalamic releasing and inhibitory hormones (factors) into the tissue fluids. These hormones are immediately absorbed into the capillaries of the hypothalamic-hypophysial portal system and carried directly to the sinuses of the anterior pituitary gland.

(To avoid confusion, the student needs to know the difference between a “factor” and a “hormone.” A substance that has the actions of a hormone but that has not been purified and identified as a distinct chemical compound is called a factor. Once it has been so identified it is thereafter known as a hormone instead of simply a factor.)

Function of the Releasing and Inhibitory Hormones. The function of the releasing and inhibitory hormones is to control the secretion of the anterior pituitary hormones. For each type of anterior pituitary hormone there is usually a corresponding hypothalamic releasing hormone; for some of the anterior pituitary hormones there is also a corresponding hypothalamic inhibitory factor. For most of the anterior pituitary hormones it is the releasing hormone that is important; but, for prolactin, an inhibitory hormone probably exerts most control. The hypothalamic releasing and inhibitory hormones (or factors) that are of major importance are:

1. Thyroid-stimulating hormone releasing hormone (TRH), which causes release of thyroid-stimulating hormone

2. Corticotropin -releasing (CRF), which causes release of adrenocorticotropin

3. Growth hormone releasing hormone (GHRH), which causes release of growth hormone, and growth hormone inhibitory hormone (GHIH), which is the same as the hormone somatostatin and which inhibits the release of growth hormone

4. Luteinizing hormone releasing hormone (LRH), which causes release of both luteinizing hormone and follicle-stimulating hormone – this hormone is also called gonadotropin-releasing hormone (GnRH)

5. Prolactin inhibitory factor (PIF), which causes inhibition of prolactin secretion

In addition to these more important hypothalamic hormones, still another excites the secretion of prolactin, and several hypothalamic inhibitory hormones inhibit some of the other anterior pituitary hormones. Each of the more important hypothalamic hormones will be discussed in detail at the time that the specific hormonal system controlled by them is presented in this and subsequent chapters.

Other Hypothalamic Substances That May Have Hormonal Effects. Multiple other substances, especially many small peptides, are found in the neurons of the hypothalamus. However, functions for these as hormones are only speculative. Yet, because they are of research interest they are listed here: (1) substance P, (2) neurotensin, (3) angiotensin II, (4) enkephalins, (5) endorphins, (6) uasoactive inhibitory polypeptide, and (7) cholecystokinin-8. Many of these same substances are also found ieurons elsewhere in the brain, suggesting that they may function as neurotransmitters both in the hypothalamus and elsewhere. In addition, some of them are in the neurons of the enteric nervous system of the gastrointestinal tract, functioning there also as neurotransmitters possibly as hormones released into the circulating blood from the nerve endings.

Thyroid Gland.

(1 and 2) Thyroxine and triidothyronine: increase the rates of chemical reactions in almost all cells of the body, thus increasing the general level of body metabolism.

(3) Calcitonin: promotes the deposition of calcium in the bones and thereby decreases calcium concentration in the extracellular fluid.

Islets of Langerhans in the Pancreas.

Insulin: promotes glucose entry into most cells of the body, in this way controlling the rate of metabolism of most carbohydrates.

Insulin

(2) Glucagon: increases the release of glucose from the liver into the circulating body fluids.

Ovaries.

(1) Estrogens: stimulate the development of the female sex organs, the breasts, and various secondary sexual characteristics.

(2) Progesterone: stimulates secretion of “uterine milk” by the uterine endometrial glands; also helps promote development of the secretory apparatus of the breasts.

Testes.

(1) Testosterone: stimulates growth of the male sex organs; also promotes the development of male secondary sex characteristics.

Parathyroid Gland.

(1) Parathormone: controls the calcium ion concentration in the extracellular fluid by controlling (a) absorption of calcium from the gut, (b) excretion of calcium by the kidneys, and (c) release of calcium from the bones.

Placenta.

(1) Human chorionic gonadotropin: promotes growth of the corpus luteum and secretion of estrogens and progesterone by the corpus luteum.

(2) Estrogens: promote growth of the mother’s sex organs and of some of the tissues of the fetus.

(3) Progesterone: probably promotes development of some of the fetal tissues and organs; helps promote development of the secretory apparatus of the mother’s breasts.

(4) Human somatomammotropin: probably promotes growth of some fetal tissues as well as aiding in the development of the mother’s breasts.

The Thyroid Metabolic Hormones

The thyroid gland, which is located immediately below the larynx on either side of and anterior to the trachea, secretes two significant hormones, thyroxine and triiodothyronine, that have a profound effect on the metabolic rate of the body. It also secretes calcitonin, an important hormone for calcium metabolism.

FUNCTIONS OF THE THYROID HORMONES IN THE TISSUES

The thyroid hormones have two major effects on the body: (1) an increase in the overall metabolic rate, and (2) in children, stimulation of growth.

GENERAL INCREASE IN METABOLIC RATE

The thyroid hormones increase the metabolic activities of almost all tissues of the body (with a few notable exceptions such as the brain, retina, spleen, testes, and lungs). The basal metabolic rate can increase to as much as 60 to 100 per cent above normal when large quantities of the hormones are secreted. The rate of utilization of foods for energy is greatly accelerated. The rate of protein synthesis is at times increased, while at the same time the rate of protein catabolism is also increased. The growth rate of young persons is greatly accelerated. The mental processes are excited, and the activity of many other endocrine glands is often increased. Yet despite the fact that we know all these many changes in metabolism under the influence of the thyroid hormones, the basic mechanism (or mechanisms) by which the hormones function is much less well known.

EFFECT OF THYROID HORMONE ON GROWTH

Thyroid hormone has both general and specific effects on growth. For instance, it has long been known that thyroid hormone is essential for the metamorphic change of the tadpole into the frog. In the human being, the effect of thyroid hormone on growth is manifest mainly in growing children. In those who are hypothyroid, the rate of growth is greatly retarded. In those who are hyperthyroid, excessive skeletal growth often occurs, causing the child to become considerably taller than otherwise. However, the epiphyses close at an early age so that the duration of growth, and the eventual height of the adult, may be shortened.

An important effect of thyroid hormone is to promote growth and development of the brain during fetal life and for the first few years of postnatal life. If the fetus does not secrete sufficient quantities of thyroid hormone, growth and maturation of the brain both before birth and afterward are greatly retarded. Without specific thyroid therapy within days or weeks after birth, the child will remain mentally deficient throughout life.

REGULATION OF THYROID HORMONE SECRETION

To maintaiormal levels of metabolic activity in the body, precisely the right amount of thyroid hormone must be secreted all the time, and to provide this, specific feedback mechanisms operate through the hypothalamus and anterior pituitary gland to control the rate of thyroid secretion. These mechanisms can be explained as follows:

Effects of Thyroid-Stimulating Hormone on Thyroid Secretion. Thyroid-stimulating hormone (TSH), also known as thyrotropin, is an anterior pituitary hormone, a glycoprotein with a molecular weight of about 28,000.

Hypothalamic Regulation of TSH Secretion by the Anterior Pituitary – Thyrotropln-ReleasIng Hormone (TRH)

Electrical stimulation of multiple areas of the hypothalamus increases the anterior pituitary secretion of TSH and correspondingly increases the activity of the thyroid gland. This control of anterior pituitary secretion is exerted by a hypothalamic hormone, thyrotropin-releasing hormone TRH), which is secreted by nerve endings in the median eminence of the hypothalamus and then transported from there to the anterior pituitary in the hypothalamic-hypophysial portal blood. The precise nuclei of the hypothalamus that are responsible for causing secreting of TRH in the median eminence are not known. However, injection of radioactive antibodies that attach specifically to TRH have shown this hormone to be present in many different hypothalamic loci, including the (1) dorsomedial nucleus, (2) suprachiasmatic nucleus, (3) ventromedial nucleus, (4) anterior hypothalamus, (5) preoptic area, and (6) paraventricular nucleus.

Insulin, Clucagon, and Diabetes Mellitus

The pancreas, in addition to its digestive functions, secretes two important hormones, insulin and glucagon. The purpose of this chapter is to discuss the functions of these hormones in regulating glucose, lipid, and protein metabolism, as well as to discuss briefly the two diseases – diabetes mellitus and hyperinsulinism—caused, respectively, by hyposecretion of insulin and excess secretion of insulin.

INSULIN AND ITS METABOLIC EFFECTS

Insulin was first isolated from the pancreas in 1922 by Banting and Best, and almost overnight the outlook for the severely diabetic patient changed from one of rapid decline and death to that of a nearly normal person.

Historically, insulin has been associated with “blood sugar,” and, true enough, insulin does have profound effects on carbohydrate metabolism. Yet, it is mainly abnormalities of fat metabolism, causing such conditions as acidosis and arteriosclerosis that are the usual causes of death of a diabetic patient. And, in patients with prolonged diabetes, the inability to synthesize proteins leads to wasting of the tissues as well as many cellular functional disorders. Therefore, it is clear that insulin affects fat and protein metabolism almost as much as it does carbohydrate metabolism.

EFFECT OF INSULIN ON CARBOHYDRATE METABOLISM

Immediately after a high carbohydrate meal, the glucose that is absorbed into the blood causes rapid secretion of insulin, which we shall discuss in detail later in the chapter. The insulin in turn causes rapid uptake, storage, and use of glucose by almost all tissues of the body, but especially by the liver, muscles, and adipose tissue. Therefore, let us discuss each of these.

Effect of Insulin on Promoting Liver Uptake, Storage, and Use of Glucose

One of the most important of all the effects of insulin is to cause most of the glucose absorbed after a meal to be stored almost immediately in the liver in the form of glycogen. Then, between meals, when food is not available and the blood glucose concentration begins to fall, the liver glycogen is split back into glucose, which is released back into the blood to keep the blood glucose concentration from falling too low.

Actions on cellular and metabolic level

The mechanism by which insulin causes glucose uptake and storage in the liver includes several almost simultaneous steps:

1. Insulin inhibits phosphorylase, the enzyme that causes liver glycogen to split into glucose. This obviously prevents breakdown of the glycogen that is already in the liver cells.

2. Insulin causes enhanced uptake of glucose from the blood by the liver cells. It does this by increasing the activity of the enzyme glucokinase, which is the enzyme that causes the initial phosphorylation of glucose after it diffuses into the liver cells. Once phosphorylated, the glucose is trapped inside the liver cells, because phosphorylated glucose cannot diffuse back through the cell membrane.

3. Insulin also increases the activities of the enzymes that promote glycogen synthesis, including phosphofructokinase that causes the second stage in the phosphorylation of the glucose molecule and glycogen synthetase that is responsible for polymerization of the monosaccharide units to form the glycogen molecules.

Effect Of INSULIN ON FAT METABOLISM

Though not quite as dramatic as the acute effects of insulin on carbohydrate metabolism, insulin also affects fat metabolism in ways that, in the long run, are perhaps equally as important. Especially dramatic is the long-term effect of insulin lack in causing extreme atherosclerosis, often leading to heart attacks, cerebral strokes, and other vascular accidents. But, first, let us discuss the acute effects of insulin on fat metabolism.

Effect of Insulin on Protein Synthesis and Storage. During the few hours following a meal when excess quantities of nutrients are available in the circulating blood, not only carbohydrates and fats but proteins as well are stored in the tissues; insulin is required for this to occur. The manner in which insulin causes protein storage is not as well understood as the mechanisms for both glucose and fat storage. Some of the facts known are:

1. Insulin causes active transport of many of the amino acids into the cells. Among the amino acids most strongly transported are valine, leucine, isoleucine, tyrosine, and phenylalanine. Thus, insulin shares with growth hormone the capability of increasing the uptake of amino acids into cells. However, the amino acids affected are not necessarily the same ones.

2. Insulin has a direct effect on the ribosomes to increase the translation of messenger RNA, thus forming new proteins. In some unexplained way, insulin “turns on” the ribosomal machinery. In the absence of insulin the ribosomes simply stop working, almost as if insulin operates an “on-off” mechanism.

3. Over a longer period of time insulin also increases the rate of transcription of DNA in the cell nuclei, thus forming increased quantities of RNA. Eventually, it also increases the rate of formation of new DNA and thus promotes reproduction of cells. All these effects promote still more protein synthesis.

4. Insulin also inhibits the catabolism ofproteins, thus decreasing the rate of amino acid release from the cells, especially from the muscle cells. Presumably this results from some ability of the insulin to diminish the normal degradation of proteins by the cellular lysosomes.

5. In the liver, insulin depresses the rate of gluconeogenesis. It does this by decreasing the activity of the enzymes that promote gluconeogenesis. Since the substrates most used for synthesis of glucose by the process of gluconeogenesis are the plasma amino acids, this suppression of gluconeogenesis conserves the amino acids in the protein stores of the body.

CONTROL OF INSULIN SECRETION

Formerly, it was believed that insulin secretion is controlled almost entirely by the blood glucose concentration. However, as more has been learned about the metabolic functions of insulin for protein and fat metabolism, it has been learned that blood amino acids and other factors also play important roles in controlling insulin secretion.

Stimulation of Insulin Secretion by Blood Glucose. At the normal fasting level of blood glucose of 80 to 90 mg/dl, the rate of insulin secretion is minimal – in the order of 25 ng/min/kg (600 (xUnits/min/kg) of body weight. If the blood glucose concentration is suddenly increased to a level two to three times normal and is kept at this high level thereafter, insulin secretion increases markedly in two stages.

1. Insulin secretion increases almost tenfold within 3 to 5 minutes after acute elevation of the blood glucose; this results from immediate dump ing of preformed insulin from the beta cells of the islets of Langerhans. However, this initial high rate of secretion is not maintained; instead, it decreases about halfway back toward normal in another 5 to 10 minutes.

2. After about 15 minutes, insulin secretion rises a second time, reaching a new plateau in 2 to 3 hours, this time usually at a rate of secretion even greater than that in the initial phase. This secretion result both from additional release of preformed insulin and from activation of some enzyme system that synthesizes and releases new insulin from the cells.

Relationship between Blood Glucose Concentration and Insulin Secretion Rate. As the concentration of blood glucose rises above 100 mg/dl of blood, the rate of insulin secretion rises rapidly, reaching a peak some 10 to 30 times the basal level at blood glucose concentrations between 400 and 600 mg/dl. Thus, the increase in insulin secretion under a glucose stimulus is dramatic both in its rapidity and in the tremendous level of secretion achieved.

Neural regulation

a) Development of somatic nerves system (Spinal cord develops faster than other parts of nervous system. In the later period of embrio, columna vertebralis grows faster then spinal cord. In newborns, the length of spinal cord is 14-16 santimetres, to 10 years it double. The main tracts of spinal cord have myelin sheaths. At the moment of birth of baby medulla oblongata is rather developed, the bigger part of nuclei thalamici is developed, the striopalidal system is developed rather good. Cortex of hemisphere cerebri has the same construction as adults one. However, during the first months of life the development of cortex goes in very fast speed. The development of the nuclei of hypothalamus is finished during the teenagers period. Frontal parts of the cortex mature the most later.)

b) Reflectory activity of fetus (After one week of fetus life begins to form reflector arc of spinal cord. When it will be the stimulation of fetus, it will be quick movement of arm, trunk, or generelazing moving reaction. That is why it presents irradiation in central nervous system, analysis of irritation. In the 9-10 weeks of fetus life present moving reaction in the case of stimulation of proprioreceptors. In 11,5 week are present seizing reactions, in 14 week beginning rythmical movement of breathing muscles. The tone of flexor muscles is increase.)

c) Development of somatic reflexes in children (Iewborns tone of flexor muscles are more then tone of extensor muscles. In 1-2 months the tone of extensor muscles are more. In 3-5 months the tone of flexor and extensor muscles are balansed. These depend from the development of corpus striatum and pyramidal system. Oriental reflexes, autonomic vision, seing are inborn. The last reflex present from a middle of 3 month to 3,5 month. We can understand that child may see. Iewborn present moving reflectory reaction, which is present in the case of stimulation of vestibular apparatus, present reflex of snatch to 3-6 month. To 5 years present reflex of Babinsky – straightening out the toes in the case of stimulation of outer part of sole. Iewborns are present stretch reflexes (they are increase from 6 to 12 month). In newborns are present suck reflex (to the end of 1 yae). Iewborns are present uncoordinating moving of arms, legs, head. In 1-1,5 month of newborn life may support the head in vertical position. From 6-7 month the infant may seat, from 10 month it may seat with different position. It may standing in the 10 month independently. Near one year baby may stand up and going.)

d) Peculiarities of electroencephalogram in children (Subcortical structures may mature earlier than cortex. Slowly activity of electroencephalogram may registrated in newborns. The alpha-rythm may registrated from 3 month, but only from 6 years it becomes main. From 6-8 years present teta-rythm (cortex-subcortex connection). In 10-12 years alpha-rethm is the same as in adult. From 12 to 15 years decrease the frequency of alpha-rethm.)

e) Changes of nervous system in old persons (In old person the weight of brain decrease, the gyrus become thin, the sulcus is broadened and deepened, ventricles of brain become broadened. Quantity of neurons decrease and glial cells increase. In old person increase the quantity of lipophyscin (product of oxidation of unsaturated fatty acids). Decrease the excitability, the speed of transmition of excitement, synaptic transmition, quantity of receptors, activity of Na-K-ATPase, permeability of membrane cannels, inhibitory processes. On electroencephalogram alpha-rythm is slow, increase teta and delta-rythms.)

f) Peculiarities of autonomic regulation (On early stages of postnatal period of regulation of inner organs take place sympathetic nervous system. Tone of parasympathetic nervous system is low, and include in providing of some reflex reaction from 2 to 3 month. The influence of autonomic system on different organs more strong on digestive tract (parasympathetic part), hart (sympathetic part) iewborns. Iewborns ganglion transmition act by help of adrenergic system. In old person’s influence of autonomic system decrease.)

The Thymus

The thymus is located in the upper part of the chest. It is made of two lobes that join in front of the trachea. The thymus is an important part of children’s immune systems. It grows larger until puberty and then begins to shrink. The gland produces thymosins, which are hormones that stimulate the development of antibodies. The thymus also produces T-lymphocytes which are white blood cells that fight infections and destroy abnormal cells.

The thymus gland is very active in childhood. It plays a crucial role in developing and improving a child’s immune system. The main thymus gland function is to produce and process lymphocytes or T cells (in T cells ‘T’ stands for thymus derived). Lymphocytes are White Blood Cells (WBCs), which are also known as leukocytes. After the white blood cells mature, they leave the thymus gland and get settled in the spleen and the lymph nodes, where a fresh batch of T cells is produced. These white blood cells are the body’s immune system and protect the body by producing antibodies that stop the invasion of foreign agents, bacteria and viruses. These cells also ensure the proper functioning of the body system and look after the wear and tear of the organs. Another function of thymus gland is to prevent the abnormal growth of cells, that may lead to cancer. The T lymphocytes travel from the bone marrow to the thymus gland where they remain until they get activated. After maturity, the lymphocytes enter the blood stream. From there they travel to other lymphatic organs and provide defense mechanism against diseases. The thymus gland also produces a hormone called thymosin, which stimulates the T cells in the other lymphatic organs to mature. This gland also produces another hormone called thymopoietin, which is protein present in the mRNA (messenger RNA) and is encoded by the TMPO gene.

In some cases, the thymus gland may become underactive. The individual may have a weak immune system and be prone to many infections and allergies. These infections can be chronic and may continue for a long time. When there is a lack of T cells in the body, it can lead to immunodeficiency diseases. The person suffering from immunodeficiency diseases may show symptoms like extreme sweating, puffiness or soreness of the throat, swelling in the glands and depression. Malnutrition and a deficiency of protein, at an early age, can lead to the slow or limited growth of the thymus, thus impairing the normal functioning of the lymphocytes. Thus ensure that your child eats a well balanced meal and also has the right amount of proteins.

Thymus Cancer

Cancer of the thymus is very rare.

Most of the time there are no symptoms of thymus cancer but the following could indicate thymus cancer.

· A cough that doesn’t go away

· Chest pain

· Trouble breathing

The thymus contains different types of cells, each of which can develop into different types of cancer:

Epithelial cells give the thymus its structure and shape. They can give rise to thymomas and thymic carcinomas, which are the main focus of the rest of this document.

Lymphocytes make up most of the rest of the thymus. Whether in the thymus or in other parts of the body, these immune system cells can develop into cancers called Hodgkin disease and non-Hodgkin lymphomas, which are described in other documents from the American Cancer Society

Kulchitsky cells, or neuroendocrine cells, are much less common cells that normally release certain hormones. These cells can give rise to cancers called carcinoid tumors. Much of the information in the American Cancer Society documents Lung Carcinoid Tumor and Gastrointestinal Carcinoid Tumors also applies to carcinoids of the thymus.

Doctors can tell the different thymic cancers apart by how they look under the microscope and by the results of other lab tests done on tissue samples.

Hormonal regulation

a) Functioning of pituitary, adrenal, sex and thyroid glands (Pituitary glands of newborns has weight 0,1-0,15 gram and increase to 10 years to 0,3 gram, to 16 year is 0,7 gram. In old person it decreases. In 16 week of fetus life produced gonadotropins which need for differenciation of sex organs. They increase in sex micturation period. Growth hormon regulate growth from 2 to 18 years (lenth of bones). Quantity of antidiuretic hormon iewborns less. The cortex of adrenal glands is more develope than medulla iewborns. To 6-8 years sex hormones do not produced. Male sex glands begin to produce the hormons from 3 month of embrion life; it stopped to the end of embrion life. They begin to produce in the period of sex micturation in female, and second time produce in the period of sex micturation in male. Maximal production of hormones produces of male in 25-35 years, and then they slowly decrease; in female sex hormones produced to the period of the end of menstruation. Thymus increase to the age 3-5 years, more intensivity grows is in 11-15 years. After 30 years it decreases in size, but increase production of glucocorticoids, sex hormones. Secretion of thiroid hormones are more in children, then in adult (maximal production in the first week of newborn life and in 12-15 years.)

b) Sex development (This is the process of forming reproductive function of organism. In female it stopped to 16-18 years, in male – to 18-20 years. There are 3 stages of sex development: prepubertate (increase the size of testis in male, increase the size of mammaliar glands in female), pubertate (to the first pollution in male and first menstruation in female), postpubertate (to the junior acne and growth of hears on face in male).)

Ovary

c) Climacteric period in female (Climacteric period is the physiological period of transmition from sex development to stopped the generative function. Climacteric period in female is from 45 to 60 years and characterizated by process of slowly decrease menstruation, hormonal function of ovarium on the fone of common age change of organism. There are two period of climacteric period. First fase of climacteric period – the fase of climacteric disfanction of ovarium or premenopausa. This period is in 45 years. The menstrual cycle from 2-fases becomes one-fases. Second period of climacteric period – postmenopausa – characterizated by whole absent of functioning of yellow body, decrease of production of estrogens and stopping the menstrual function.)

d) Climacteric period in male (Climacteric period in male determined by age involutive processes, which are present in sex glands and are from 50 to 60 years. The quantity of testosterons and androgens decrease and honadotropic hormones is increase. This process may be with clinic picture of climacteric period, but in the biggest part of male the climacteric manifistations are absent.)

Testicle

Students` practical Activities:

Influence of melanocytestimulating hormone on pigment cells of swimming membrane of a frog.

Fix a narcotized frog on a table. Stretch the swimming membrane above the hole of the table and observe it under the small magnification of a microscope. Pay attention to the condition of pigment cells. Introduce 0,2 ml of melanocyte stimulating hormone into spinal lymphatic sack. Evaluate the color of the animal and the condiiton of pigment cells in 20 min.

The influence of epinephrine on the size of pupilla

Compare the diameter of pupilla in both eyes of the examinie. Than put 1-2 drops of epinephrine 0,1 % into conjuctival sack. Observe the size of pupillas during 20-30 minutes.

Evaluation of the parathyroid glands condition

a) Chvostek’s test

Make some light knockings by a neurological hammer in front of meatus acustius externus. If the functions of parathyroid glands are damaged the contraction of the muscles that are innervated by the VII nerve is observed.

b) Veis’ test

Make some light knockings on the lateral margin of the orbita where there is a zygomatical branch of the nervus facialis. If the functions of parathyroid glands are damaged the contraction of the musculus orbicularis oculi is observed.

c) Trusso’s test

Press the brachium by turniquet pulse will disappear for 2-3 minutes. If the functions of parathyroid glands are damaged the titanic contraction of manual muscles is observed.

Influence of the insulin on the glucose adoption

Take two white mice with the same weight. Introduce intraperitoneal 1.5-2.0 ml of 20 % glucose solution. Give subcutaneal insulin to one mouse. To pick up the urine during one hour.

Make an investigation of the urine for the glucose. Filtrate 3 ml urine. Make a Feling’s reaction for the glucose. Compare the resultates.

References:

1. Review of Medical Physiology // W.F. Ganong. – Twentieth edition, 2001. – P. 233-242, 307-368, 383-438.

2. Textbook of Medical Physiology // A.C. Guyton, J.E. Hall. – Tenth edition, 2002. – P. 684, 706, 836-844, 846-856, 858-865, 869-880, 884-894, 899-910, 916-926, 929-939, 948-950, 958-959, 965-966.