ROLE OF ENDOCRINE GLANDS IN THE REGULATION OF ORGANISM‘S FUNCTIONS

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.

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

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

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.

(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 maintain normal 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 (In newborns 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. In newborn 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. In newborns are present stretch reflexes (they are increase from 6 to 12 month). In newborns are present suck reflex (to the end of 1 yae). In newborns 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.)

Type 1 diabetes.

When the pancreas fails to produce enough insulin, type 1 diabetes (pronounced: dy-uh-be-teez and previously known as juvenile diabetes) occurs. In kids and teens, type 1 diabetes is usually an autoimmune disorder, which means that some parts of the body's immune system attack and destroy the cells of the pancreas that produce insulin. To control their blood sugar levels and reduce the risk of developing diabetes problems, kids and teens with this condition need regular injections of insulin.

Type 2 diabetes.

Unlike type 1 diabetes, in which the body can't produce normal amounts of insulin, in type 2 diabetes the body can't respond to insulin normally. Kids and teens with the condition tend to be overweight. Some kids and teens can control their blood sugar level with dietary changes, exercise, and oral medications, but many will need to take insulin injections like people with type 1 diabetes.

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 in newborns less. The cortex of adrenal glands is more develope than medulla in newborns. 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).)

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.)

Hyperthyroidism.

Hyperthyroidism (pronounced: hi-per-thy-roy-dih-zum) is a condition in which the levels of thyroid hormones in the blood are very high.

In kids and teens, the condition is usually caused by Graves' disease, an immune system problem that causes the thyroid gland to become very active. Doctors may treat hyperthyroidism with medications, surgery, or radiation treatments.

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.