Lecture 10-11: Hypothalamus and Endocrinology (1) PDF

ENDOCRINOLOGY 1 1.Hypothalamus and Pituitary glands For many years, the pituitary gland was considered the “master” endocrine gland because it secretes several hormones that control other endocrine glands. The pituitary...

ENDOCRINOLOGY 1 1.Hypothalamus and Pituitary glands For many years, the pituitary gland was considered the “master” endocrine gland because it secretes several hormones that control other endocrine glands. The pituitary gland is about the size of a small grape and has two lobes: 1. a larger anterior pituitary or anterior lobe 2. a smaller posterior pituitary or posterior lobe 2 3 3 4  The pituitary glands composed of three lobes: Anterior, intermediate, and posterior lobes The intermediate lobe is rudimentary in human. The anterior lobes secretes 6 well known hormones. The posterior lobes releases 2 hormones. 5 5 6  Hormones secreted from the anterior lobe of the pituitary gland 7 7 Posterior Pituitary Hormones The posterior pituitary contains the axons and axon terminals of more than 10,000 neurosecretory cells whose cell bodies are in the hypothalamus. Although the posterior pituitary does not synthesize hormones, it does store and release two hormones. In the hypothalamus, the hormones oxytocin (oxytoc- = quick birth) and antidiuretic hormone (ADH) are synthesized and packaged into secretory vesicles within the cell bodies of different neurosecretory cells. Nerve impulses that arrive at the axon terminals trigger release of these hormones into the capillaries of the posterior pituitary 8  Oxytocin Chemical structure: Nano-peptide Mode of action: binds to membrane receptors and activate second messenger. Effects: During and after delivery of a baby, oxytocin has two target organs: the mother’s uterus and breasts. During delivery, oxytocin enhances contraction of smooth muscle cells in the wall of the uterus. After delivery, it stimulates milk ejection (“letdown”) from the mammary glands in response to the mechanical stimulus provided by a suckling infant. Together, milk production and ejection constitute lactation. The function of oxytocin in males and in non-pregnant females is not clear. 9 Antidiuretic Hormone (ADH) An antidiuretic (anti- = against; diuretic = urine-producing agent). Chemical structure: Nano-peptide Mode of action: binds to membrane receptors and activate second messenger. Hormone Effects: ADH causes the kidneys to retain more water, thus decreasing urine volume. In the absence of ADH, urine output increases more than tenfold, from the normal 1–2 liters to about 20 liters a day. ADH also decreases the water lost through sweating and causes constriction of arterioles. This hormone’s other name, vasopressin (vaso- = vessel; pressin- = pressing or constricting), reflects its effect on increasing blood pressure. The amount of ADH secreted varies with blood osmotic pressure and blood volume. 10  Anterior Pituitary Hormones The anterior pituitary synthesizes and secretes hormones that regulate a wide range of bodily activities, from growth to reproduction. Secretion of anterior pituitary hormones is stimulated by releasing hormones and suppressed by inhibiting hormones, both produced by the hypothalamus. The hypophyseal portal veins deliver the hypothalamic releasing 11 and inhibiting hormones from the hypothalamus to the anterior Human Growth Hormone (GH) Chemical structure: Protein Mode of action: through synthesis and secretion of small protein hormones called insulin-like growth factors (IGFs) or somatomedins. Effects: 1. stimulate protein synthesis, help maintain muscle and bone mass, and promote healing of injuries and tissue repair. 2. Enhance breakdown of triglycerides (fats), which releases fatty acids into the blood, 3. Breakdown of liver glycogen, which releases glucose into the blood. 4. Cells throughout the body can use the released fatty acids and glucose for the production of ATP. 5. Decrease protein catabolism and transport of AA into the cells (muscles). 12  Stimulation of GH Inhibition of GH Growth hormone – releasing Somatostatin hormone (GH-RH) Hypoglycemia * (insulin) Hyperglycemia Falling free fatty acids Rising free fatty acids Rising amino acids (arginine, Somatomedins (via somatostatin leucine) stimulation) Fasting, starvation Growth hormone Stages 3 and 4 of sleep Cortisol Stress Pregnancy Exercise Obesity Glucagon β-adrenergic agonists Estrogens, androgens Dopamine, acetylcholine, serotonin 13 α-Adrenergic agonists 13 Endocrinopathies: Disorders associated with increased GH Overproduction of GH during adolescence results in gigantism, which is characterized by excessive growth of the long bones. 14 14  15 15 Excessive GH secretion during adulthood, after the epiphysial (growth) plates of long bones have fused, causes growth in those areas where cartilage persists. This leads to acromegaly, a condition characterized by: coarse facial features, prominent brow, enlarged hands and feet, and soft tissue hypertrophy (e.g., cardiomegaly, hepatosplenomegaly, and renomegaly). 16 16  Acromegaly 17 17 Disorders associated with decreased GH Decreased GH secretion in immature persons leads to stunted growth, or dwarfism, which accompanied by sexual immaturity, hypothyroidism, and adrenal insufficiency. GH deficiency may be part of an overall lack of anterior pituitary hormones (panhypopituitarism) or from an isolated genetic deficiency. 18 18  19 19 Haalloooooooo!!! 20 20  Prolactin (PRL): Chemical structure: Protein Mode of action: binds to membrane receptors and activate second messenger Effects: Together with other hormones, initiates and maintains milk production by the mammary glands. During pregnancy, very high levels of estrogens promote secretion of prolactin-releasing hormone (PRH), which in turn stimulates release of prolactin. 21 22  Thyroid-stimulating hormone (TSH): Chemical structure: Glycoprotein Mode of action: binds to membrane receptors and activate second messenger Effects: Increase iodine uptake by thyroid cells. Stimulates the synthesis and secretion of thyroid hormones by the thyroid gland ( T3 and T4). 23 Adrenocorticotropic hormone (ACTH): Chemical structure: Polypeptide Mode of Action: binds to membrane receptors and activate second messenger. Effects: ACTH or corticotrophin controls the production and secretion of hormones called glucocorticoids by the cortex (outer portion) of the adrenal glands. Corticotrophin-releasing hormone (CRH) from the hypothalamus stimulates secretion of ACTH. Stress-related stimuli, such as low blood glucose or physical trauma, and interleukin-1, a substance produced by macrophages, also stimulate release of ACTH. Glucocorticoids cause negative feedback inhibition of both CRH and 24 ACTH release.  Follicle-stimulating Hormone (FSH) and Luteinizing Hormone (LH) Chemical structure: Glycoproteins Mode of action: binds to membrane receptors and activate second messenger Effects: In females, the ovaries are the targets for follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Each month FSH initiates the development of several ovarian follicles and LH triggers ovulation. After ovulation, LH stimulates formation of the corpus luteum in the ovary and the secretion of progesterone (sex hormone) by the corpus luteum. 25 FSH and LH also stimulate follicular cells to secrete estrogens. In males, FSH stimulates sperm production in the testes, and LH stimulates the testes to secrete testosterone. Gonadotropin-releasing hormone (GnRH) from the hypothalamus stimulates release of FSH and LH. The release of GnRH, FSH, and LH is suppressed by estrogens in females and by testosterone in males through negative feedback systems. 26  Melanocyte-stimulating Hormone (MSH): Chemical structure: Polypeptide Mode of action: binds to membrane receptors and activate second messenger. Effects: There is little level of circulating MSH in humans. Although an excessive amount of MSH causes darkening of the skin, the function of normal levels of MSH is unknown. The presence of MSH receptors in the brain suggests it may influence brain activity. Excessive corticotropin-releasing hormone (CRH) can stimulate MSH release, and dopamine inhibits MSH release. 27 TABLE 13.2 Summary of Pituitary Gland Hormones and Their Actions HORMONE ACTIONS Anterior Pituitary Hormones Human Stimulates liver, muscle, cartilage, bone, and other tissues to synthesize and secrete growth hormone (hGH) insulinlike growth factors (IGFs); IGFs promote growth of body cells, protein synthesis, tissue repair, breakdown of triglycerides, and elevation of blood glucose level Thyroid-stimulating hormone (TSH) Stimulates synthesis and secretion of thyroid hormones by the thyroid gland In females, initiates development of oocytes and induces secretion of estrogens by the Follicle-stimulating hormone (FSH) ovaries; in males, stimulates testes to produce sperm In females, stimulates secretion of estrogens and progesterone, ovulation, and formation of Luteinizing hormone (LH) corpus luteum; in males, stimulates testes to produce testosterone Prolactin (PRL) In females, stimulates milk production by the mammary glands Adrenocorticotropic hormone (ACTH), Stimulates secretion of glucocorticoids (mainly cortisol) by the adrenal cortex also known as corticotropin Melanocyte-stimulating hormone Exact role in humans is unknown but may influence brain activity; when present in excess, (MSH) can cause darkening of skin Posterior Pituitary Hormones Oxytocin Stimulates contraction of smooth muscle cells of uterus during childbirth; stimulates milk Antidiuretic hormone (ADH), also ejection from mammary glands known as vasopressin Conserves body water by decreasing urine output; decreases water loss through sweating; raises blood pressure by constricting (narrowing) arterioles 28  Thyroid gland 29 29 2. THYROID GLAND: The butterfly-shaped thyroid gland is located just below the larynx (voice box). It is composed of right and left lobes, one on either side of the trachea. Chemical structure: Amino acids derivatives (iodothyronine). Mode of action: bind to receptors in the nucleus. Microscopic spherical sacs called thyroid follicles make up most of the thyroid gland. 30  The wall of each thyroid follicle consists primarily of cells called follicular cells, which produce two hormones: Thyroxine, also called (T4) because it contains four atoms of iodine. Triiodothyronine (T3) which contains three atoms of iodine. T3 and T4 are also known as thyroid hormones. A smaller number of cells called Para follicular cells lie between the follicles, that produce the hormone calcitonin. 31 Actions of Thyroid Hormones Because most body cells have receptors for thyroid hormones, T3 and T4 exert their effects throughout the body. 1. Thyroid hormones increase basal metabolic rate (BMR), the rate of oxygen consumption under standard or basal conditions (awake, at rest, and fasting). As cells use more oxygen to produce the ATP, more heat is given off, and body temperature rises. In this way, thyroid hormones play an important role in the maintenance of normal body temperature. 2. The thyroid hormones also stimulate protein synthesis, 3. increase the use of glucose and fatty acids for ATP production, 4.increase the breakdown of triglycerides, and enhance cholesterol excretion, thus reducing blood cholesterol level. 5. Together with human GH and insulin, thyroid hormones stimulate body growth, particularly the growth of the nervous and skeletal systems. 32  & 33 Goiter Any enlargement of the thyroid gland is called a goiter, and antithyroid substances that cause thyroid enlargement are called goitrogens. Goitrogens are substances that block the synthesis of thyroid hormone. 34 34 Goiter 35 35 Hypothyroidis 36 m  Hyperthyroidis m Grave's disease 37 3. Para thyroid gland The Calcitropic Hormones: Parathyroid Hormone, Calcitonin, and Vitamin D 38 38  The parathyroid glands (para-=beside) are small, round masses of glandular tissue that are partially embedded in the posterior surface of the thyroid gland. Usually, one superior and one inferior parathyroid gland are attached to each thyroid lobe. Within the parathyroid glands are secretory cells called chief cells that release a.parathyroid hormone (PTH). PTH is the major regulator of the levels of calcium (Ca2+), magnesium (Mg2+), and phosphate (HPO42- ) ions in the blood. PTH increases the number and activity of osteoclasts, which break down bone extracellular matrix and release Ca2+ and HPO42- into the blood. 39 b.Calcitonin The hormone produced by the parafollicular cells of the thyroid gland is calcitonin (CT). Calcitonin can decrease the level of calcium in the blood by inhibiting the action of osteoclasts, the cells that break down bone. The secretion of calcitonin is controlled by a negative feedback system. Calcitonin’s importance in normal physiology is unclear because it can be present in excess or completely absent without causing clinical symptoms. 40  4.PANCREATIC ISLETS The pancreas is a flattened organ located in the curve of the duodenum, the first part of the small intestine. It has both endocrine functions and exocrine functions. The endocrine part of the pancreas consists of clusters of cells called pancreatic islets or (islets of Langerhans). Some of the islet cells, the alpha cells, secrete the hormone glucagon, and other islet cells, the beta cells, secrete insulin. 41 Abdominal aorta Celiac trunk Spleen (elevated) PANCREAS Duodenum of small intestine Anterior view Blood capillary Exocrine cells Alpha cell(secretes glucagon) Beta cell (secretes insulin) 42  Anatomical and histolgical consideration The endocrine pancreas consists of islets of langerhans, which form 2% of the pancreatic tissue. Each islet consists of approximately 3000 cells. The human endocrine pancreas consists of approximately one million islets. Four types of cells have been identified in the endocrine pancreas : 43 43 a. Alpha cells make up about 25% of the islet cells and are the source of glucagon which consists of 29 amino acid residues. b. Beta cells constitute about 60% of the islet cells and are associated with insulin synthesis. This polypeptide consists of 51 amino acid residues. c. Delta cells form about 10% of the islet cells and are the source of somatostatin which is a tetradecapeptide. d. Pancreatic polypeptide (PP or F) cells form approximately 5% of the islet cells and synthesize a polypeptide that contains 36 amino acid residues. 44 44 Control of secretions The alpha, beta, and delta cells constitute a functional syncytium, which forms a paracrine control system for the coordinated secretion of pancreatic polypeptides. a. Insulin inhibits alpha cell secretion (glucagon), thereby increasing peripheral glucose uptake and opposing glucagon- mediated glucose production (gluconeogenesis). 45 45 b. Glucagon stimulates beta cell secretion (insulin) and delta cell secretion (somatostatin) leading to hypoglycemia, which, in turn, increases hepatic glucose production and opposes hepatic glucose storage. c. Somatostatin inhibits alpha cell (glucagon) and beta cell (insulin) secretion, producing hypoglycemia and inhibition of intestinal glucose absorption. d. PP inhibits insulin and somatostatin secretion via a direct pancreatic effect. 46 46  General Actions of Glucagon and Insulin The main action of glucagon is to increase blood glucose level when it falls below normal, which provides neurons with glucose for ATP production. Insulin, by contrast, helps glucose move into cells, especially into muscle fibers, which lowers blood glucose level when it is too high. Therefore, insulin is an important hormone when tissues are developing, growing, or being repaired. 47 Diabetes Mellitus Diabetes mellitus is a syndrome of impaired carbohydrate, fat, and protein metabolism caused by either lack of insulin secretion or decreased sensitivity of the tissues to insulin. There are two general types of diabetes mellitus: 1. Type I diabetes, also called insulin-dependent diabetes mellitus (IDDM), is caused by lack of insulin secretion. 2. Type II diabetes, also called non–insulin-dependent diabetes mellitus (NIDDM), is caused by decreased sensitivity of target tissues to the metabolic effect of insulin. This reduced sensitivity to insulin is often called insulin resistance. In both types of diabetes mellitus, metabolism of all the main foodstuffs is altered. The basic effect of insulin lack or insulin resistance on glucose metabolism is to prevent the efficient uptake and utilization of glucose by most cells of the body, except those of the brain. As a result, blood glucose concentration increases, cell utilization of glucose falls increasingly lower, and utilization of fats and proteins increases. 48  49 Adrenal gland 50 50  5.ADRENAL GLANDS There are two adrenal glands, one lying atop each kidney. Each adrenal gland has regions that produce different hormones: the outer adrenal cortex, which makes up 85 percent of the gland, and the inner adrenal medulla. 51 Mineralocorticoids Aldosterone: Aldosterone: it regulates homeostasis of two mineral ions, namely, sodium ions (Na+) and potassium ions (K+). Aldosterone increases reabsorption of Na+ from the fluid that will become urine into the blood, and it stimulates excretion of K+ into the fluid that will become urine. It also helps adjust blood pressure and blood volume, and promotes excretion of H+ in the urine. Secretion of aldosterone occurs as part of the renin– angiotensin– aldosterone pathway. Conditions that initiate this pathway include dehydration, Na+ deficiency, or hemorrhage, which decrease blood volume and blood pressure. 52  Glucocorticoids The most abundant glucocorticoid is cortisol. Cortisol and other glucocorticoids have the following actions: 1. Protein breakdown: increase the rate of protein breakdown. 2. Glucose formation by the liver 3. Breakdown of triglycerides in adipose tissue. 4. Anti-inflammatory effects: inhibit white blood cells that participate in inflammatory responses. 5. Depression of immune responses: glucocorticoids are prescribed for organ transplant recipients to decrease the risk of tissue rejection by the immune system. 53 Hyperfunctional lesions: Cushing's syndrome Major clinical manifestations include the following: Increased cortisol secretory rate. Hypertension due to Na+ retention Insulin resistance (hyperglycemia due to gluconeogenesis and hyperinsulinemia). Weight gain Muscle wasting and weakness Mental liability, depression, irritability, psychosis, manic depression. 54 54  Women: oligomenorrhea or amenorrhea, decreased libido Men: decreased Libido impotency. 55 55 Cushing's syndrome 56  Adrenal Medulla Hormones The adrenal medulla, consists of sympathetic postganglionic cells of the autonomic nervous system (ANS) that are specialized to secrete hormones. The two main hormones of the adrenal medullae are epinephrine and norepinephrine (NE), also called adrenaline and noradrenaline, respectively. 1. These two hormones greatly augment the fight-or-flight response: Epinephrine and norepinephrine increase the pumping output of the heart, which increases blood pressure. 2. They also increase blood flow to the heart, liver, skeletal muscles, and adipose tissue; dilate airways to the lungs; and increase blood levels of glucose and fatty acids. 3. Like the glucocorticoids, epinephrine and norepinephrine also help the body resist acute stress (fight-or-flight). 57