-Ahmad Rawajbeh. -Dania alkouz. -Saleem Khresha. 1 P a g e

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1 -2 -Ahmad Rawajbeh -Dania alkouz -Saleem Khresha 1 P a g e

2 The information marked with "(+)" has not been mentioned during the lectures. I added them to clarify and explain. The pituitary gland (+) From pituita phlegm(mucus). Taken as the name for the gland because it was believed that it secreted mucus to the nose. It's also called the hypophysis gland/ (+)physis=growth hypophysis cerebri outgrowth under the brain. a master gland because it's controlled by the hypothalamus ( the king of human body ) which is affected by all centers of the brain. a small gland (less than 1gram, less than 1cm in diameter) and secrete many hormones. Located in a cavity at the base of brain called Sella Turcica. Controls the secretion of many hormones. Composed of two lobes: 1. Anterior pituitary: also called adenohypophysis, indirectly connected with the hypothalamus. 2. Posterior pituitary: also called neurohypophysis, directly connected with the hypothalamus. (+)Adeno=glandular/adenohypophysis is truly glandular. It produces its own hormones and releases them into the circulation. Neurohypophysis it contains nerve endings storing secretory granules filled with hormones synthesized in the cells bodies that lie in the hypothalamus ***These two parts are different in their embryology, histology, and physiology. 2 P a g e

3 The posterior pituitary lobe It has a direct connection with the hypothalamus. Neurons (called magnocellular neurons) extend from the hypothalamus down to the posterior pituitary gland; these neurons produce hormones in their bodies. then the hormones are packed in secretory granules and transported down the axons ( axoplasm )to the nerve endings located in the posterior pituitary gland, they remain there and released when the neurons are stimulated. So, the function of the posterior pituitary gland is just to store hormones synthesized by the hypothalamus (contain the nerve ending which contain the hormone). These hormones are called neurohormones because they are produced by nerve cell bodies. These neurohormones are produced by two nuclei: the paraventricular nucleus which produces oxytocin and a little bit of ADH (antidiuretic hormone), and the supraoptic nucleus which produces ADH and a little bit of oxytocin. (+)Each of these nuclei can synthesize about one sixth as much of the second hormone as of its primary hormone. (+)the posterior pituitary is derived from a neural tissue outgrowth from the hypothalamus. is composed mainly of glial-like cells called pituicytes. they do not secrete hormones. Instead, they support large numbers of nerve endings from neurons come from the hypothalamus ADH and Oxytocin are stored in the posterior pituitary. And released into the blood in response to signals coming from the hypothalamus. The type of secretion is neuroendocrine. Each nucleus secretes one of the two hormones mainly and a little bit of the other. Why? Because there are similarities in the structure between these two hormones, and a little bit similarity in the function. 3 P a g e

4 Posterior pituitary hormones 1. Oxytocin. 2. ADH (vasopressin). Reminder(required): from the summer course of biochemistry: Vasopressin and Oxytocin are cyclic peptides due to a disulfide bond Both are composed of nine amino acids and they differ from each other in just two amino acids. Both have an amide group at the c-terminal end. The sequence of their amino acids is : NH3-Gly-Tyr-X-Gln-Asn-Cys-Pro-Y-Gly-N X represents Ile in Oxytocin and Phe in ADH. Y represents Leu in Oxytocin and Arg in ADH. **The posterior pituitary in human produces Arginine Vasopressin. Some other mammals also produce Lysine Vasopressin(Arginine replaced by Lysine). As they have similar structure(differ from each other in only two amino acids), they have little similarities in function: Both increase water reabsorption in the kidneys, but ADH is 200 times more potent than Oxytocin. Both increase milk ejection as well, but Oxytocin is 100 times more potent. ADH mainly increases water reabsorption. Oxytocin mainly increases milk ejection and induces contraction of the 4 P a g e

5 pregnant uterus. The Antidiuretic hormone (ADH, Vasopressin) Functions: 1. Normalize the blood volume as well as body fluid volume (regulates serum osmolarity) by increasing the reabsorption of water in the nephrons 2. Vasoconstriction of the blood vessels. ** these are the two main functions but the ADH receptors on nephrons differ from those on the blood vessels. Two names and two main functions: Antidiuretic Hormone decreases diuresis (production of urine)/v2 receptors Vasopressin constriction of blood vessels/ V1 receptors 3. In addition, it increases sweating. Stimulators: 1-Increased serum osmolarity 2-Decreased extracellular fluid volume 3-Stress-related factors: nausea, pain, vomiting, nicotine, opiates (analgesic drugs like morphine), and hypoglycemia. 4-Anti-neoplastic drugs. Inhibitors: 1-Ethanol 2-α-Adrenergic agonists. 3-Atrial natriuretic peptide (hormone from the atria of the heart). 4-decreased serum osmolarity. Anterior pituitary lobe: It is indirectly connected with the hypothalamus by the hypothalamichypophyseal portal system. (+)It is derived from Rathke s pouch which is an embryonic invagination of the pharyngeal epithelium. This explains the epithelioid nature of its cells compared to the posterior lobe (+)It is highly vascular with extensive capillary sinuses among the 5 P a g e

6 glandular cells. Almost all the blood that enters these sinuses passes first through another capillary bed in the median eminence (the lowermost portion of the hypothalamus). The blood then flow through portal blood vessels to supply the anterior lobe of the pituitary gland. The nerve cell bodies in the hypothalamus produce hormones that inhibit or stimulate the anterior pituitary. These hormones released from the hypothalamus into the a capillary bed (in the median eminence). When the neurons of the hypothalamus are stimulated, the nerves endings release the hormones into the blood where they are transported to stimulate or inhibit the secretion of anterior pituitary hormones. Secretion of anterior pituitary hormones is regulated through two pathways: 1. The short pathway when hormones packed in secretory granules from the hypothalamus extend down through neurons to the posterior pituitary. From that location, they are released into hypothalamichypophysial short portal vessels, then to the anterior pituitary to stimulate or inhibit it. The long pathway when hormones from the hypothalamus are released in the median eminence, then through hypothalamic- 6 P a g e

7 hypophysial long portal vessels to the anterior pituitary. Anterior pituitary gland hormones When you take a section from the anterior pituitary and stain it, you will find that in the section, there are at least 5 cell types can be differentiated. Each cell type produces major hormone (non -tropic : GH, prolactin and tropic : ACTH, FSH, LH, TSH ) *Tropic means : affect other endocrine glands 1. Somatotropes: cells release growth hormones GH (somatotropin) 2. Corticotropes: cells release adrenocorticotropic hormones ACTH 3. Thyrotropes: cells release thyroid stimulating hormones TSH 4. Gonadotropes: cells release follicle-stimulating hormones and Luteinizing hormones FSH, LH. 5. Lacotropes(mammotropes): cells release prolactin. 7 P a g e

8 (+) when staining these cells, Somatotropes and Lacotropes ( which produce non-tropic hormones GH and prolactin ) are acidophilic cells while the other three types of cells ( which produce tropic hormones FSH, LH, ACTH, TSH ) are basophilic. About 30-40% of the cells are somatotropes (secreting GH), 20% are corticotropes (secreting ACTH), and each of the other cells account for 3-5% of the total. Nevertheless, they secrete powerful hormones that control thyroid functions, sexual functions, and milk production. Normally separate cells produce prolactin and growth hormones. However, some normal and tumor cells produce both. GH is a singlechain polypeptide that is homologous with prolactin Gonadotropes produce both FSH and LH. It is found that in normal and abnormal condition, there are separate cells that produce each one of them. 8 P a g e

9 Hormones of hypothalamus that cause secretion or inhibition of anterior pituitary hormones: 1. Corticotropin Releasing Hormone (CRH) that stimulate corticotropes releasing ACTH. 2. Thyrotropin Releasing Hormone (TRH) that stimulate thyrotropes releasing TSH. 3. Growth Hormone Releasing Hormone (GHRH) that stimulate somatotropes releasing GH. 4. Growth Hormone Inhibitory Hormone (GHIH/Somatostain) that stimulate somatotropes inhibiting GH. 5. Gonadotropin Releasing Hormone (GnRH) that stimulate gonadotropes releasing LH and FSH. 6. Prolactin inhibiting hormone (PIH/Dopamine) that inhibit prolactin releasing from lactotropes. Most of these Hormones stimulate the anterior pituitary gland, except prolactin inhibiting hormone, why? Because inhibiting is more important than stimulating since prolactin is not needed in male cells, and even in female cells it's not needed all the time (only, during pregnancy and breast feeding). (+)it doesn t mean that the hypothalamus doesn t produce a stimulatory hormone for prolactin. In fact, it produces releasing hormone but the inhibitory hormone probably exerts more control. Growth hormone secretion is controlled by inhibitory and stimulatory hormones. The other hormones just have stimulatory hormones, why? Because their secretions are inhibited by negative feedback mechanisms The hypothalamus receives signals from all the centers of the CNS. All the hypothalamus hormones are peptides except the dopamine (a catecholamine). TRH has the shortest amino acids sequence (3). GHRH has the longest amino acids sequence (44) 9 P a g e

10 Growth hormone(somatotropin): It is a small protein molecule that contains 191 amino acids in a single chain and has a molecular weight of 22,005. It causes growth of almost all tissues of the body that are capable of growing. It promotes increased sizes of the cells and increased mitosis. It is the most important hormone for normal growth to adult size. Somato=body, tropin= stimulation stimulation of body growth. (+)All the other hormones affect target glands (thyroid, adrenal cortex, ovaries, testicles, and mammary glands) The mammary glands are exocrine glands not endocrine which are the target of prolactin, so it is a non-tropic hormone This figure shows the effect of growth Hormone rats, 2 rats: the first one is a normal rat and the second one is injected with growth hormone. Notice how growth increase drastically in the second rat. Hormonal interactions: 1. Permissive: presence of one hormone is required for other hormone to exert or enhance its effect. 2. Synergism: when many hormones complement each other and function together to produce effects greater than sum of their individual effects. effect(x+y) > effectx + effecty 3. Antagonism: when a hormone opposes the action of another ( 10 P a g e

11 insulin- glucagon) Growth hormone is not the only hormone that stimulate growth in the body. Many hormones stimulate growth synergistically: 1. Insulin like growth factor(somatomedin) 2. Androgen 3. Insulin 4. Thyroid Hormone 5. Glucocorticoid hormone 6. Estrogen Growth hormone and insulin-like growth factor have been identified as the major determinants of the growth in the normal life (normal post uterine life). The absence of each of the other hormones seriously affect the normal growth of the musculoskeletal system as well as maturation and growth of the other tissues. GH and insulin: GH and insulin work together synergistically. In a rat without pancreas and without pituitary, the growth was minimal. First the rat is injected with GH, the growth slightly increases. Then it is injected with insulin the increase was very little but more than that with GH (insulin has stronger effect than GH). After injecting the rat with GH and insulin together, the weight of this rat increased. The effect of GH and Insulin in combination is more than the sum of their effects when each one is used alone. ( > 2 ) Growth hormone has direct effect and indirect effect on growth. 1. Direct effect on: A. The adipose tissue: it decreases the adiposity, by increasing the lipolysis and decreasing the glucose uptake by tissues ( decrease insulin ). ( increase blood concentration of free fatty acids and glucose ) 11 P a g e

12 B. Liver cells: it increases: 1- RNA synthesis to increase protein production. 2- The rate of protein synthesis. 3- Gluconeogenesis (production of glucose from non-carbohydrate sources). C. Muscles cells: It decreases glucose uptake (glucose remain in the blood), increase amino acid uptake to the tissues and increase protein synthesis. So, it directly decreases glucose uptake and increases lipolysis, protein synthesis in muscles increasing the lean body mass, and production of somatomedin. 2. Indirect effect: Through Somatomedin (insulin like growth factor): Several hormones that are different in the number and the arrangement of their amino acids, they differ in their potencies as well. They are secreted in response to GH by the liver. They affect bone, heart, lungs, kidneys, pancreas, intestines, parathyroid, skin, connective tissue, chondrocytes(cartilage) to increase their protein synthesis, cell size and number. Growth hormone enhances body protein directly or indirectly, decreases fat stores, and conserves carbohydrate stores. Increase rate of growth = increase rate of protein synthesis. Diabetogenic effect of growth hormone (due to abnormal /over release of growth hormone): Excessive secretion of growth hormone has two effects: 1-It increases glucose level causing hyperglycemia which increases insulin secretion indirectly. 2-It directly increases insulin secretion from the beta cells of the pancreas. Excess secretion of GH for long time makes beta cells(insulinsecreting cells) over stimulated and burned out, then it will cause diabetes mellitus type 2(non-insulin dependent). Under this 12 P a g e c

13 ondition, excessive amount of fat is mobilized. Then, the liver produces great amount of acetoacetic acid (ketone bodies) release into the body fluids which in turn causes ketosis ( ketogenis effect ) this also causes fatty liver Diabetogenic effect of other anterior pituitary hormones: Growth hormone is not the only anterior pituitary hormone that increases the blood glucose concentration. At least three others can do the same: 1-Adrenocorticotropin (ACTH) 2-Thyroid-stimulating hormone (TSH) 3-Prolactin ACTH is especially important as it increases the rate of cortisol secretion by the adrenal cortex. cortisol then increases the blood glucose concentration by increasing the rate of gluconeogenesis. Dietary factors that affect these hormones secretion: 1. protein intake: GH, somatomedin, and insulin increase. 2. carbohydrate intake: we don't need growth hormone or somatomedin. insulin will increase to normalize blood glucose level. 3. fasting: we don't need insulin or somatomedin. GH will increase to supply glucose and free fatty acid. Factors affecting the secretion of GH: Growth hormone is secreted in a pulsatile pattern, increasing and decreasing. The precise mechanisms that control secretion of growth hormone are not fully understood, but several factors related to a person s state of nutrition or stress are known to stimulate secretion. Stimulators: 1 decreased blood glucose 2 decreased blood fatty acids 3 Increased blood amino acids (arginine) 4 Starvation or fasting protein deficiency 5 Trauma, stress, excitement exercise 6 Testosterone, estrogen 7 Deep sleep (stages II and IV). 13 P a g e

14 8 Growth hormone-releasing hormone(ghrh) 9 Ghrelin by the intestines and the stomach Inhibitors: 1 Increased blood glucose 2 Increased blood free fatty acids 3 Aging 4 Obesity 5 Growth hormone inhibitory hormone (somatostatin)/blocks the response of the anterior pituitary to the GHRH. 6 Growth hormone (exogenous) 7 Somatomedins (insulin-like growth factors)/either directly on the anterior pituitary or indirectly by stimulating the secretion of somatostatin from the hypothalamus. 14 P a g e

15 Negative feedback mechanisms: 1-GH inhibits its own secretion: -by stimulating the secretion of somatomedin which stimulates somatostatin secretion -by stimulating the secretion of somatostatin directly. 2-GHRH inhibits its own secretion directly. ( ultra-short loop ) 15 P a g e

16 This figure shows the developmental rhythm of GH secretion. GH levels are higher in children than adults with a peak period during puberty. GH secretion declines with aging. Feedback mechanism for control food intake: 1. Stretch receptors in the stomach activate sensory afferent pathway through vagus nerve and inhibit food intake. 2. Peptide YY, cholecystokinin(cck), and insulin are gastrointestinal hormones that are released by ingestion of food and suppress further feeding. 3. Ghrelin is released by the stomach and the intestines, especially during fasting and stimulates eating. 4. Leptin hormone is released in high amounts by fat cells as they increase in size, it inhibits food intake. 16 P a g e

17 summary The pituitary gland(hypophysis) is a master gland divided into two lobes: Anterior lobe(adenohypophysis) secrets six major hormones: GH, ACTH, TSH, LH, FSH, and Prolactin. The Posterior lobe(neurohypophysis) secrets two major hormones: Oxytocin and ADH (arginine vasopressin) All pituitary secretion is controlled by either hormonal (ant. lobe) or nervous signals (post. lobe) from the hypothalamus which acts as a collecting center for information concerning the internal well-being of the body ADH is primarily synthesized in the supraoptic nucleus, while the oxytocin is primarily synthesized in the paraventricular nucleus. ADH normalizes extracellular fluid volume and causes vasoconstriction. ADH is stimulated in response to decreased serum osmolarity, stress, antineoplastic drugs, etc. it is inhibited by alcohol, α-adrenergic drugs, and the atrial natriuretic peptide. The hypothalamus controls the activity of the anterior pituitary by several hormones released into hypothalamic-hypophysial portal vessels transporting them to the anterior pituitary. CRH, TRH, and GnRH stimulate the secretion of the corresponding hormones. Prolactin is usually inhibited by dopamine. GH is controlled by stimulatory and inhibitory(somatotropin) hormones GH directly or indirectly stimulates growth in all tissues capable of growth. Many other hormones stimulate growth synergistically such as insulin, estrogen, somatomedin, and thyroid hormone. GH directly decreases glucose uptake and increases lipolysis, protein synthesis in muscles increasing the lean body mass, and production of somatomedin. It indirectly enhances protein synthesis in many tissues by stimulating somatomedin secretion. Excess GH cause hyperglycemia, ketosis, fatty liver, insulin resistance, and type 2 diabetes mellitus. TRH, prolactin, and ACTH have diabetogenic effects as well. ACTH stimulates cortisol. GH is stimulated in response to decreased blood glucose, decreased blood fatty acids, Increased blood amino acids (arginine), fasting protein deficiency, trauma, stress, excitement exercise testosterone, estrogen deep sleep (stages II and IV), and growth hormone-releasing hormone(ghrh). It is inhibited by Increased blood glucose level Increased blood free fatty acids, aging, obesity, growth hormone inhibitory hormone (somatostatin), and somatomedins. Feeding suppressed by CCK, peptide YY, insulin, leptin, and stretch receptors on the stomach. Ghrelin is released from the intestines and the stomach during fasting to stimulate eating. 17 P a g e

18 TEST 1-The hypothalamus gland secrets several hormones into a capillary bed in the median eminence. These hormones stimulate or inhibit the secretion of anterior pituitary hormones (e.g. GH). A blood sample from this bed was taken. Then, the hormones were isolated and treated with SDS. Gel electrophoresis was carried on the hormones. Which of the following hormones most likely forms the lowest band? (A) Growth hormone releasing hormone. (B) Corticotropin releasing hormone. (C) Growth hormone inhibitory hormone. (D) Thyrotropin releasing hormone. 2-Which of the following hormones originates in the anterior pituitary? (A) Dopamine (B) Growth hormone releasing hormone (GHRH) (C) Somatostatin (D) Gonadotropin-releasing hormone (GnRH) (E) Thyroid-stimulating hormone (TSH) 3-Which of the following inhibits the secretion of growth hormone by the anterior pituitary? (A) Sleep (B) Stress (C) Puberty (D) Somatomedins (E) Starvation 18 P a g e

19 4-A neuroscientist is studying communication between the hypothalamus and pituitary in a rat model. She interrupts blood flow through the median eminence and then measures circulating levels of pituitary hormones following appropriate physiologic stimulation. Secretion of which of the following hormones will be unaffected by the experimental manipulation? (A) Growth hormone (B)Prolactin (C) Thyroid-stimulating hormone (D) Follicle-stimulating hormone (E) Vasopressin 5-During childbirth, a woman suffers a serious hemorrhage and goes into shock. After she recovers, she displays symptoms of hypopituitarism. Which of the following will not be expected in this patient? (A) Cachexia (B) Infertility (C) short stature (D) Low basal metabolic rate (E) weight loss 6-Which of the following is true regarding GH? (A) GH secretion is stimulated directly by the somatomedin (B) All the negative feedback pathways of GH end in somatotropin stimulation which in turn decreases GH secretion from the anterior pituitary (C) GH is a peptide hormone stimulated by GHRH from the hypothalamus (D) GH is the only pituitary hormone that is inhibited by hypothalamic hormones. (E) GH stimulates growth of all tissues in the body (F) More than one or none of the above 19 P a g e

20 7-Which of the following stimulates GH secretion? (A) Alcohol. (B) Methyldopa. (C) Morphine. (D) Phenylephrine. (E) None of the above. 8-Which of the following hormones has no significant diabetogenic effects? (A) Adrenocorticotropic hormone (B) Thyroid stimulating hormone (C) Prolactin (D) Cortisol (E) Oxytocin 9-Which one of the following hormones produced from lipid? (A) Somatostatin (B) Dopamine (C) Follicle stimulating hormone (D) Lysine vasopressin (E) Cortisol 10-Growth hormone is controlled by a diurnal rhythm. When during the day GH is high in amount? (A) During sleep (B) After waking up. (C) During 1st few hours of deep sleep (D) During strenous exercise. 20 P a g e

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