Unit 24 - Endocrine System


The endocrine system is the second of the major integrating systems, the nervous system being the first. Along with the nervous system, this it ties together all of the other body system thereby integrating the body into a functioning whole.


A. Description - The endocrine system consists of a series of ductless glands which produce chemical regulators known as hormones. The hormones are released directly into the circulation and are carried to the tissues which they affect (target tissues) by the blood.


B. Function - The endocrine system, like the nervous system, functions in control, communication, and integration. It aids in the coordination of the activities of all of the bodies's cells.


C. Comparison with the nervous system - In regards to the integration function, it is convenient to thing of the nervous system and endocrine system as being the opposite sides of the same regulatory coin. They both have the same overall functions, but they execute them in different ways.


1. Target tissues


a. Nervous system - Muscles and nervous tissues.


b. Endocrine system - Muscle, nervous tissue, and virtually all non-excitable tissues as well.


2. Mode of action


a. Nervous system - This is a digital or on-off system in which information is coded in the pathway and frequency of the action potentials.


b. Endocrine system - This is an analog or concentration dependent system. Hormones alter cellular metabolism and the effects produced are dependent upon the concentration of the hormone in the blood.


3. Response speed and duration


a. Nervous system - Rapid response and rapid termination of the response are characteristic.


b. Endocrine system - Response time is slower, but the response is usually much longer lasting.


4. Field of control


a. Nervous system - Much of the nervous system is devoted to responding to the external environment although it also responds to internal changes as well.


b. Endocrine system - This is almost exclusively an internal control system. Responses to the external environment are indirect and usually mediated by the nervous system.


5. Relationship - The nervous system and endocrine system interact with one another. Hormones affect nervous activity and nervous activity affects hormone release. The bulk of the endocrine system is ultimately controlled by the nervous system. As a consequence, both systems work in concert with one another.


D. Hormones


1. Definition (endocrine hormone)- A chemical substance secreted by one cell with its site of action at a distant cell (target cell) where it serves to regulate metabolic reactions.


a. Local hormones - These are chemical regulators that don't meet the classical definition of an endocrine hormone. There are two general classes.


(1) Paracrines - These regulators are normally released by adjacent cells. Prostaglandins and neurotransmitters are examples.


(2) Autocrines - These are substances released by a cell which affects the cell which released them. Il-2 is an example.


2. Chemical classes - Hormones fall into four chemical classes.


a. Steroids - These are derived from a precursor molecule known as cholesterol. They include the hormones of the adrenal cortex and the gonads.


b. Biogenic amines - These are the simplest of the hormones and consist of modified amino acids. Examples include the thyroid hormone, thyroxine, and two catecholamine hormones, epinephrine and norepinephrine.


c. Peptides and proteins - These hormone consist of chains of amino acids. In size they range from three to about 200.


d. Eicosanoids - These are local hormones (paracrines and autocrines) and are derived from the fatty acid arachidonic acid. They include the prostaglandins, leukotrienes, and thromboxanes.


E. Mechanisms of hormone action - There are several events involved in hormone action.


1. Recognition of target cells - Hormones are released into the blood and will therefore come in contact with every cell in the body. Only target cells will be affected. The target cell has an appropriate receptor, a molecule that the hormone can attach to.


a. Receptor molecules are usually proteins or proteins with a polysaccharide component (glycoproteins).


b. Receptors may be attached to the surface of the cell membrane or may actually be inside of the cell.


c. It is the interaction of the hormone and the receptor that determine the effects of the hormone on the cell.


d. Receptors are not constant static features but rather frequently change in response to the hormonal environment.


(1) Up-regulation - This is an increase in the number of receptors on a target cell in response to decreased levels of hormone. It makes the cell more sensitive to the hormone.


(2) Down-regulation - This represents a decrease in the number of receptors on a target cell that is exposed to high levels of a hormone. It results in a decrease in sensitivity of the target cell.


2. Transport of hormones in the blood - The water soluble hormones (catecholamines, peptides, and proteins) circulate freely in the plasma. Most of the lipid soluble steroid hormones and the thyroid hormones are bound to transport proteins. These proteins have three functions.


a. They make the lipid soluble hormones temporarily water soluble.


b. Minimize hormone loss by kidney filtration.


c. Establish a reserve of hormone. There exists an equilibrium between found and free hormone in the plasma. Usually 0.1 to 10% of the steroid hormones are present in the free fraction. This is the fraction that can diffuse out of the capillaries and bind to target cells.


3. General effects of hormones - There are five general actions that hormones mediate.


a. Alteration of membrane permeability and/or membrane potential.


b. Synthesis of protein.


c. Activation and inactivation of enzymes.


d. Initiation of secretion by cells.


e. Stimulation of cell division.


4. Biochemical effects of hormones on target cells - There appear to be two major means by which hormones exert their influence. One, known as the fixed receptor model, applies to water soluble hormones and utilizes a second intracellular messenger. The other mechanism applies to the lipid soluble hormones and relies upon gene activation.



a. Fixed receptor model - This model explains how a hormone which normally cannot pass through the cell membrane can affect reactions which occur inside of the cell. Most protein derived hormones attach to a receptor located on the outside of the cell membrane and in doing so activate a "second messenger" inside of the cell. The hormone serves as the "first messenger" and activates the "second messenger."


b. G-proteins - The hormone receptors do no attach directly to adenyl cyclase. The surface receptors are linked directly to the adenyl cyclase by means of molecules known as G-proteins. G-proteins are the intramembrane mediators for most second messenger systems. These include not only hormones, but other signaling molecules such as many of the neurotransmitters.



(1) Cyclic AMP -In many cases the second messenger is the compound cyclic AMP, which is derived from ATP. The sequence of events is as follows.


(a) The hormone (first messenger) binds with the receptor site on the outside of the cell membrane.


(b) The binding activates the enzyme adenyl cyclase which is attached to the inside of the cell membrane.


(c) Activated adenyl cyclase catalyzes the conversion of ATP into cyclic AMP (second messenger). After a short period of time, a second enzyme, phosphodiesterase, inactivates cAMP.


(d) Cyclic AMP activates certain inactive proteins known as kinases. Kinases are a class of proteins that activate other proteins by phosphorylating them. They cleave a phosphate group from ATP and transfer it to the inactive protein, thereby causing its activation. Most of these proteins are enzymes. It is important to note that this system does not cause the production of new proteins, but only the activation of inactive forms which already exist.


(2) Calcium - This ion often serves as a second messenger itself, and in other cases functions to activate other second messengers.


(a) The first messenger activates a G protein which in turn activates phospholipase C . This enzyme generates two second messengers, diacyglycerol (DAG) and inositol triphosphate (IP3.


(b) IP3 triggers the release of calcium stored inside of the cytoplasm as for example in the smooth ER of many cells.


(c) DAG plus intracellular calcium activate the membrane protein protein kinase C. This then phosphorylates membrane calcium channels allowing calcium to flow into the cell.


(d) The calcium usually combines with the protein calmodulin. This activates calmodulin which then activates specific cytoplasmic enzymes.

(3) There are also inhibitory G proteins which when activated cause a reduction in second messenger inside of the cell.


c. Gene activation (genetic induction) - This is the mechanism by which the steroid and thyroid hormones exert their influence. These hormones pass readily through the cell membrane and into the nucleus where they bind with receptors. The activated receptor then turns on genes resulting in the synthesis of new protein. Usually the new proteins are enzymes that will modify the physiology of the cell.


F. Control of hormone secretion - As a rule, hormones are released in short bursts. Generally there is very little secretion between bursts. There are three major stimuli that bring on these bursts.


1. Action potentials from the nervous system.


2. Chemical changes in the plasma and extracellular fluids.


3. Other hormones.


The individual control mechanisms will be discussed in more detail with specific hormones.


G. Hypophysis (Pituitary gland) - A small gland about one cm in diameter which is located in the floor of the cranium. It is suspended from the hypothalamus of the brain by a stalk known as the infundibulum. In humans it is divided into two parts, the adenohypophysis and the neurohypophysis, the infundibulum is actually part of the neurohypophysis.


1. Adenohypophysis (anterior lobe) - This lobe produces seven hormones all of which are protein or protein derived. Many of these hormones have other endocrine glands as their target tissues.


a. Relationship to hypothalamus - A portal system connects the nervous tissue of the hypothalamus with the non-nervous tissue of the adenohypophysis. This portal system is termed the adenohypophyseal hypothalamic portal system. The hypothalamus exercises control over the adenohypophysis by means of chemicals which it releases into the portal system.


b. Releasing and inhibiting hormones - These are the chemical substances which are produced by the nerve cells of the hypothalamus. They are transported to the target cells of the adenohypophysis by the portal system. They either inhibit or stimulate the release of the adenohypophyseal hormones. Chemically these factors are small peptide chains. All of the adenohypophyseal hormones have a releasing hormone and at least three of them have an inhibiting hormone as well.


c. Adenohypophyseal hormones - There are seven of these hormones. All are polypeptide/proteins. Four of them control other endocrine glands and are referred to as tropic hormones.


(1) Gonadotropins - These constitute two of the seven hormones and they principally affect the gonads of both males and females.


(a) FSH - Follicle stimulating hormone - In females this hormone induces follicle formation, maturation of the ovum, and the production of the sex hormone, estrogen. In males it stimulates maturation of the sperm.


(b) LH - Luteinizing hormone - In females it induces ovulation and the conversion of the ruptured follicle in the corpus luteum which produces estrogen and a second sex hormone, progesterone. In males it stimulates the Leydig cells (interstitial cells) to produce the male sex hormone, testosterone.


(c) The release of both FSH and LH is under the control of gonadotropin releasing hormone (GnRH) from the hypothalamus.


(2) Thyrotropin (Thyroid stimulating hormone - TSH) - This hormone stimulates the production and release of the thyroid hormone, thyroxine. It is controlled by thyrotropin releasing hormone (TRH).


(3) Adrenocorticotropin (Adrenocorticotropic hormone - ACTH) - This stimulates the production and release of the steroid hormones of the adrenal cortex. It is controlled by the releasing hormone, corticotropin releasing hormone (CRH).


(4) Somatotropin (Growth hormone - GH) - This hormone stimulates growth, particularly of the skeleton. Growth hormone has the following effects.


(a) It stimulates protein synthesis.


(b) It stimulates the breakdown of adipose tissue and the release of fatty acids as energy sources.


(c) It stimulates the breakdown of glycogen into glucose which results in an increase in blood sugar.


(d) Many of the effects of growth hormone are carried out by a group of peptides termed somatomedins. These are produced by the liver and are activated growth hormone.


(e) Underproduction of growth hormone during the growing period results in midgets. Over production during this period results in giantism. Over production after growth has ceased causes a condition known as acromegaly.


(f) Growth hormone is controlled by a growth hormone releasing hormone (GHRH) and an inhibiting factor known as somatostatin.


(5) Prolactin - This initiates and maintains milk secretion in females. There is no clearly defined role in males. There is a releasing hormone, PRH and an inhibiting hormone, PIH.


(6) Melanocyte stimulating hormone (MSH) - In amphibians this hormone causes darkening of the skin but its role in humans is obscure. However administration of MSH for several days does result in the darkening of the skin. MSH releasing hormone (MRH) stimulates release while MSH inhibiting hormone (MIH) blocks release.


d. Regulation of the adenohypophyseal hormone levels - The four tropic hormones (TSH, FSH, LH, and ACTH) are regulated by negative feedback loops based upon their target gland hormone level. Whenever the target gland hormone reaches its proper level, it feeds back and blocks the release of the tropic hormone's releasing hormone. The other three hormones depend upon the release of their respective inhibiting hormones.



2. Neurohypophysis - posterior lobe - This part of the hypophysis is derived embryologically from nervous tissue and therefore has a different origin than the adenohypophysis which is derived from non-nervous tissue.


a. Relationship to the hypothalamus - Axons of nerve cells which originate in the hypothalamus travel down the infundibulum and terminate in the neurohypophysis. These axons form the hypothalamic-hypophyseal tract. The nerve cells are the sites of hormone production. These specialized nerve cells are termed neurosecretory cells. The hormones are transported down the axons and released from the neurohypophysis into the blood. Action potentials on the neurosecretory cells cause hormone release.


b. Hormones - The neurohypophysis releases two hormones, ADH and oxytocin. Both of these are octapeptides.


(1) ADH - antidiuretic hormone (vasopressin) - This hormone plays a more role in water reabsorption. Its target tissue is the distal convoluted tubules and the collecting tubules of the kidney. When its concentration is high, water is reabsorbed from the urine and is conserved in the body. When its concentration is low, water is excreted is large quantities by the urine.


(a) Control of secretion - ADH levels are controlled by the osmotic concentration of the blood.


/1/ The neurosecretory cells that produce ADH are sensitive to the changing osmotic pressure of the plasma.


/2/ Increasing osmotic pressure (indicating a water deficiency) causes these cells to shrink which causes them to become active releasing large amounts of ADH. This conserves water.


/3/ Low osmotic pressure in the plasma (indicating too much water) results in a swelling of the cells as water moves into them osmotically. This causes them to swell and decrease their ADH production and release. As a result water is lost to the urine and removed from the body.


ADH can also cause an increase in blood pressure by causing vasoconstriction. This is the reason for the alternative name, vasopressin.


(2) Oxytocin - This hormone stimulates contraction of the uterine smooth muscle and is a major factor in the induction of labor. It also causes the ejection of milk from the breast. In males it stimulates the emission of prostate fluid into the male reproductive tract by stimulating contraction of smooth muscle in the prostate gland. It also appears to play a role in sexual arousal in both sexes.


(a) Control of secretion - Secretion is under nervous control. Dilation of the cervix of the uterus prior to giving birth seems to cause a reflexive release. Suckling by a baby also results in a nervous reflex which causes release. Oxytocin is inhibited by high levels of the sex hormone progesterone. This hormone is high during pregnancy.


H. Thyroid gland - This is one of the largest of the endocrine glands. It is a butterfly shaped gland that is about 5 cm long and 3 cm wide. It straddles the trachea at the base of the neck. It produces two major hormones.


1. Thyroxine - This hormone is produced by iodinating the amino acid tyrosine. There are two chemical forms. The most abundant form is termed T4 while the less common form is known as T3. Thyroxine affects virtually every cell in the body, except for brain, uterus, spleen, testes, and the thyroid. It regulates the overall metabolism, growth, and development of the body. Increases in thyroxine levels always increases the metabolic rate and heat production.


a. Control of secretion - Thyroxine is under the control of the hypothalamic-hypophyseal system. TRH from the hypothalamus causes the release of TSH by the adenohypophysis. TSH increases secretion of thyroxine by the thyroid. Negative feedback decreases its production.


b. Over secretion results in Grave's disease (Hyperthyroidism). This is an autoimmune disease. Individuals produce antibodies that mimic TSH but are not subject to normal negative feedback control. There is increased heart rate, profuse sweating, thinness, hyperactivity, bulging of eyes, and emotional instability.Surgical removal, thyroid suppressing drugs, and radioactive isotopes are all used in treating this disease.

c. Under secretion during the growth years results in cretinism. Cretins are retarded dwarfs. During the adult years hypothyroidism is referred to as myxedema. Persons suffering from this condition sleep a lot, lack energy, and are usually obese. Atherosclerosis increases. Dry skin and mental dullness are also characteristic. Treatment is by the administration of thyroxine tablets. Myxedema is five times more common in females.


d. Goiter is a condition where the thyroid enlarges. It can be associated with either under or over secretion. Hyperthyroidism and goiter may be brought about by over stimulation of the thyroid by TSH. In cases of iodine deficiency the thyroid enlargement may be due to increased TSH levels due to an absence of negative feedback by thyroxine. Goiters can be surgically corrected.


2. Calcitonin - This second hormone is a protein and is involved in calcium metabolism. It is produced by C cells in the thyroid gland. Its actions will be discussed in detail with the parathyroid glands.


I. Parathyroid glands - These consist of four minute yellow bodies, a pair embedded in each of the lateral lobes of the thyroid. They produce a hormone known as PTH.


1. PTH (Parathyroid hormone) functions to increase serum calcium levels. It has three major sites of action.


a. Bone - It stimulates the osteoclasts to demineralize bone thereby returning calcium and phosphate to the serum.


b. Kidney - PTH increases the reabsorption of calcium and magnesium from the urine and blocks the reabsorption of phosphate. The effect is to increase serum calcium and lower serum phosphate. It also stimulates the kidneys to produce calcitrol (1,25-dihydroxy cholecalciferol) which is the active form of vitamin D.


c. Intestine - Here it enhances the absorption of calcium. Vitamin D (calcitrol), a cholesterol derivative, is also necessary for absorption.


Regulation is by calcium levels in the blood. If calcium start to fall, PTH secretion increases.


2. Calcitonin - This thyroid hormone has the opposite effects of PTH. It causes a decrease in calcium levels in the plasma. Its release is also controlled by serum calcium levels. Calcitonin seems to be most important in children.


3. Summary of calcium regulation - PTH increases serum calcium while calcitonin decreases it. As calcium levels increase above normal, calcitonin levels increase and PTH levels decrease. If calcium levels fall below normal then PTH increases and calcitonin decreases.


J.  Adrenal glands - These are pyramid-shaped glands located on the superior surface of each kidney. They are embedded in fat. Each gland is actually a composite, with two distinct kinds of tissue being present. The inner portion is derived embryonically from nervous tissue and is known as the adrenal medulla. The outer portion is of non-nervous origins and is termed the adrenal cortex.


K.  Functionally they are separate glands, each producing chemically different hormones and each being controlled by different mechanisms.


1. Adrenal medulla - This gland produces a pair of chemically related hormones, norepinephrine and epinephrine, which are collectively referred to as the catecholamines. Norepinephrine affects mainly the cardiovascular system while epinephrine has both metabolic and cardiovascular effects.


a. Epinephrine - The functions of this hormone are as follows.


(1) It increases blood glucose (sugar) levels by stimulating the breakdown of glycogen in the liver. It also stimulates the conversion of muscle glycogen into lactic acid which can be used by the liver to build more carbohydrate.


(2) It increases the rate, force, and amplitude of the heart beat.


(3) It constricts blood vessels in the skin, mucous membranes, and kidneys, but it dilates blood vessels to the muscles.


b. Norepinephrine - This increases heart rate and the force of cardiac muscle contraction. It will cause constriction of the blood vessels in most of the body. Overall it causes an increase in blood pressure.


c. Overall, the effects of the catecholamines is to prepare the body for stress situations where fight or flight may be necessary. During stressful times, catecholamine levels will be highly elevated.


d. Control of release - Normally the adrenal medulla produces a mixture of about 80% epinephrine and 20% norepinephrine. Secretion is controlled by the sympathetic nervous system. As the sympathetic division and the catecholamines have the same basic affect on the various target tissues, it is useful to think of the adrenal medulla as magnifying the effects of the sympathetic division. Sometimes the adrenal medulla and the sympathetic division are considered to be one functional system, the sympatheticoadrenal system.


2. Adrenal cortex - The adrenal cortex makes up the bulk of the adrenal glands and produces steroid hormones which are derived from cholesterol. Although many cortex steroid hormones have been identified, they can all be considered to belong to three functional classes.


a. Mineralocorticoids - These hormones regulate sodium and potassium levels. They increase serum sodium levels by actively promoting reabsorption of sodium from the kidney tubules. They decrease serum potassium levels by stimulating the secretion of potassium into the urine. In addition these hormones also promote excretion of hydrogen ion in the urine and thereby prevent acidosis. The principal mineralocorticoid is aldosterone. Aldosterone secretion is controlled by the following mechanisms.


(1) Elevated serum potassium - This results in an increase of aldosterone which then reduces potassium levels.


(2) Reduced serum sodium - This also increases aldosterone levels which in turn increases sodium levels.


(3) Angiotensin - Release of renin by the kidney converts angiotensinogen into angiotensin which then increases aldosterone levels.

(4) Atrial natriuretic peptide - This hormone which is released by the atrial myocardial cells inhibits the release of aldosterone.


b. Glucocorticoids - These hormones regulate carbohydrate metabolism and resistance to stress. Their role in metabolism is to insure that enough ATP is available. They do this by:


(1) conserving glucose in the blood by causing a shift from glucose metabolism to fatty acid metabolism in the muscles.


(2) promoting gluconeogenesis, the production of glucose from non-carbohydrate sources.


They provide resistance to stress by insuring that additional quantities of ATP will be available to power all of the reactions necessary to deal with stress. They can also indirectly increase blood pressure.

In large (pharmacological) doses they suppress the inflammatory response and depress cell mediated immunity. The principal glucocorticoid is cortisol. Regulation is principally by ACTH from the adenohypophysis.


c. Sex hormones - Small quantities of both female(estrogens) and male hormones (androgens) are produced in both sexes. In females the adrenal androgens contribute to sex drive and other sexual behavior. The androgens also contribute to the development of pubic and axillary hair in both males and females.


d. Over production of cortex hormones leads to a condition known as Cushing's syndrome. Patients are flushed, obese, with deposition of fat in the upper back causing a "buffalo hump," and there is a general weakness. Osteoporosis, atherosclerosis, and edema are also common. Overproduction of adrenal androgens in females can lead to a condition known as virilism or masculinization. This can result in lowering of the voice, growth of a beard, and enlargement of the clitoris so that it resembles a penis. Atrophy of the breasts, loss of the menstrual period, and enlargement of muscles are also characteristic. In males over production of adrenal estrogens can result in gynecomastia. The principal symptom here is the enlargement of the mammary glands.


e. Underproduction of the cortex hormones leads to Addison's disease. It results in an inability to regulate blood sugar and an inability to cope with stress. Loss of aldosterone yields decreasing serum sodium and increasing serum potassium. This leads to reduced water reabsorption, low blood pressure, acidosis, and renal failure. Increased skin pigmentation also occurs and leads to a bronzed appearance. Left untreated death results from severe water and electrolyte disturbance.


K. Pancreas - This is a dual purpose gland producing both exocrine and endocrine secretions. The exocrine secretions consist of digestive enzymes. The hormones are produced by clusters of special endocrine tissue known as the Isles of Langerhans. The hormones produced are as follows.


1. Glucagon - This hormone is produced by the alpha cells. Its effect is to increase blood sugar. It does this through the following mechanisms.


a. It promotes the breakdown of glycogen by the liver.


b. It stimulates gluconeogenesis.


c. It stimulates the breakdown of fats which increase materials available for carbohydrate synthesis and it also produces ketone bodies.


2. Insulin - This hormone is produced by the beta cells. It is composed of two polypeptide chains. Its overall function is to decrease blood sugar. It causes this to happen by facilitating the transport of glucose into all of the body cells with the exception of the nervous system whose cells are insulin independent. It also stimulates lipid synthesis by converting glucose into fatty acids, stimulates glycogenesis, slows gluconeogenesis, and promotes the entry of amino acids into cells.


3. Somatostatin - This is the same polypeptide which inhibits growth hormone. It is produced by the delta cells. It is also secreted by the mucosa of the upper gastrointestinal tract. It may function to inhibit the release of both insulin and glucagon.


4. Control of release of the pancreatic hormones - There are three levels of control, chemical, hormonal, and neural.


a. Chemical - The levels of glucose seem to be the major governing factor. High blood glucose levels stimulate insulin release and inhibit glucagon release. Low blood sugars stimulate glucagon release and inhibit insulin release.


b. Hormonal - Several of the digestive hormones which function primarily in controlling digestive juices also seem to stimulate insulin release.


c. Neural - Acetylcholine from the parasympathetic nervous system stimulates insulin release. Norepinephrine and epinephrine from the sympathetic division and adrenal medulla inhibit insulin release but stimulate glucagon release.


5. Over production of insulin results in a rapid drop in blood sugar. The first symptoms are apparent intoxication followed by convulsions.


6. Underproduction of insulin leads to diabetes mellitus. This disease results in severe metabolic and fluid/electrolyte disturbances. There are two varieties of diabetes. Type I (juvenile) usually occurs before age 20 and is an autoimmune disease. Here there is normally a complete absence of insulin production and as a result insulin injections are necessary. Type II (adult onset) accounts for about 90% of a cases and usually appears after the age of 40. Frequently this form is mild and can be controlled by diet, exercise, and weight loss. Insulin is usually not the problem in type II. Rather it appears that there is a loss of sensitivity to insulin by the body cells, probably due to down regulation of insulin receptors. The sequence of events that occur in diabetes are as follows.


a. Hyperglycemia - This is elevated blood sugar. It will lead to glycosuria,or sugar in the urine. This causes an increase in osmotic pressure of the urine which results in loss of water from the body and dehydration. This is the reason that diabetics urinate frequently.


b. The loss of ability to take up sugar from the blood results in a switch to fat metabolism by most cells.


c. Fat metabolism leads to the production of fatty acids and ketone bodies. The acids result in acidosis and ketone bodies have an aromatic odor which results in the "fruity" breath characteristic of diabetics.


d. Untreated, the end result of diabetes is coma and death. This is due to acidosis of the body fluids and the loss of salts through the large quantities of urine produced.


e. There are many side effects to diabetes mellitus. These include atherosclerosis, loss of sensation, blindness, difficulty in wound healing, and loss of limbs to gangrene. It is the leading cause of blindness in the United States each year. When all of the side effects are considered, diabetes is the third leading cause of death in the United States each year.


L. Summary of the hormonal regulation of blood sugar - There are a total of five hormones involved in the regulation of blood sugar. Reviewing them provides as list as follows.


1. Growth hormone - This decreases carbohydrate utilization by cells there therefore increases blood sugar.


2. Glucocorticoids - These promote an increase in blood sugar by gluconeogenesis, especially during periods of stress.


3. Epinephrine - This causes an increase in sugar by promoting the breakdown of glycogen, especially during periods of stress.


4. Glucagon - This hormone also increases blood sugar by promoting the breakdown of glycogen.


5. Insulin - This hormone causes a decrease in blood glucose by stimulating uptake of glucose by the cells.


In the normal day by day regulation of blood sugar, glucagon and insulin are the most significant.


M. Heart - Atrial natriuretic peptide is released by the atria when they are stretched. It decreases sodium and water retention by decreasing renin and aldosterone secretion. The result is reduction in blood pressure.


N. Gonads - These organs produce the sex hormones in both sexes. The role of these hormones will be discussed with the reproductive system.


O. Digestive tract - The mucosa produces several hormones that regulate the digestive process. They were discussed previously.


P. Pineal gland - This appears to be an endocrine gland but its role in humans is ill defined. In animals it coordinates reproductive physiology and behavior with day length. It produces a hormone known as melatonin which is derived from the neurotransmitter serotonin. The pineal gland receives indirect innervation from the eyes and melatonin is only synthesized in the dark. While there has been a great deal of interest in the effects of melatonin in the popular press, its role in human physiology is not well defined. It seems to play roles in the following areas.


1. Circadian rhythms - This is the best established function. These are daily rhythms of physiological processes. These physiological events are coordinated with night and day through the action of melatonin..


2. There is some evidence that melatonin may play a role in coordinating release of sex hormones, especially at the onset of puberty. It is well known that melatonin depresses sex hormone production in other animals. Evidence indicates that their is a decrease of melatonin at the time of puberty. This may permit the production and release of the sex hormones that are responsible for the changes of puberty.


3. Melatonin is a powerful antioxidant. It may protect CNS neurons from free radicals such at nitric oxide and hydrogen peroxide.


4.  Seasonal affective disorder - This is a type of severe depression that occurs in certain people who live at high latitudes. It occurs during the winter months when light levels are very low. It has been treated by using bright lights. It may result from over production of melatonin.


Q. Thymus gland - This produces a series of polypeptides that are collectively referred to as thymosins. These convert immature lymphocytes into T-cells.


R. Kidney - Erythropoietin which stimulates red blood cell production and renin which stimulates the angiotensin system are two hormones produced by the kidney. The kidney also produces calcitrol, a hormone which is really the active form of vitamin D. This hormone aids PTH in raising serum calcium levels.


S. Adipose cells These produce a hormone called leptin. This hormone is released after the adipose cells take up glucose and lipids which they store as fat. Leptin binds with CNS neurons producing a sensation of satiety.


T. Eicosanoids - There are three groups of these, the prostaglandins, leukotrienes, and thromboxanes. All act as paracrines or autocrines. They represent chemical modifications of the 20 carbon fatty acid arachidonic acid. Nearly all body cells make the first two of these regulators. Thromboxanes are derived mainly from platelets. Following release they are rapidly inactivated.


1. Prostaglandins - These are classified into three groups, PGA, PGE, and PGF. Variations in structure are designated by subscripts, i.e. PGA2.


2. Prostaglandins have a wide variety of functions. They alter smooth muscle contraction, secretion, blood flow, reproduction, platelet function, respiration, nerve impulse transmission, fat metabolism, and immune responses. They also mediate inflammation, fever, and pain.


3. Leukotrienes stimulate chemotaxis of white blood cells and mediate inflammation.


4. Thromboxanes function in the clotting process.