Faisal I. Mohammed, MD, PhD Endocrine System L4 Faisal I. Mohammed, MD, PhD University of Jordan

Parathyroid Glands Embedded in lobes of thyroid gland, usually 4. Parathyroid hormone (PTH) or parathormone Major regulator of calcium, magnesium, and phosphate ions in the blood Increases number and activity of osteoclasts Elevates bone resorption Stimulates the conversion of 25-hydroxycholecalciferol (inactive vitamin D) into 1,25-dihydroxycholecalciferol (Active vitamin D-calcitriol) which will increase intestinal Ca++ reabsorption. Blood calcium level directly controls secretion of both calcitonin and PTH via negative feedback University of Jordan

Parathyroid Glands University of Jordan

Parathyroid Glands Embedded in the lateral lobes of the thyroid gland. Parathyroid hormone (PTH): Only hormone secreted by the parathyroid glands. Single most important hormone in the control of blood [Ca2+]. Stimulated by decreased blood [Ca2+]. Promotes rise in blood [Ca2+] by acting on bones, kidney and intestines. University of Jordan

Roles of Calcitonin, Parathyroid hormone, Calcitrol in Calcium Homeostasis University of Jordan

High level of Ca2+ in blood stimulates thyroid gland 1 High level of Ca2+ in blood stimulates thyroid gland parafollicular cells to release more CT. Low level of Ca2+ in blood stimulates parathyroid gland chief cells to release more PTH. CALCITONIN inhibits osteoclasts, thus decreasing blood Ca2+ level. PARATHYROID HORMONE (PTH) promotes release of Ca2+ from bone extracellular matrix into blood and slows loss of Ca2+ in urine, thus increasing blood Ca2+ level. 3 4 2 1 High level of Ca2+ in blood stimulates thyroid gland parafollicular cells to release more CT. Low level of Ca2+ in blood stimulates parathyroid gland chief cells to release more PTH. CALCITONIN inhibits osteoclasts, thus decreasing blood Ca2+ level. 3 2 1 High level of Ca2+ in blood stimulates thyroid gland parafollicular cells to release more CT. 1 CALCITRIOL stimulates increased absorption of Ca2+ from foods, which increases blood Ca2+ level. PTH also stimulates the kidneys to release CALCITRIOL. High level of Ca2+ in blood stimulates thyroid gland parafollicular cells to release more CT. Low level of Ca2+ in blood stimulates parathyroid gland chief cells to release more PTH. CALCITONIN inhibits osteoclasts, thus decreasing blood Ca2+ level. PARATHYROID HORMONE (PTH) promotes release of Ca2+ from bone extracellular matrix into blood and slows loss of Ca2+ in urine, thus increasing blood Ca2+ level. 3 4 2 5 6 1 PTH also stimulates the kidneys to release CALCITRIOL. High level of Ca2+ in blood stimulates thyroid gland parafollicular cells to release more CT. Low level of Ca2+ in blood stimulates parathyroid gland chief cells to release more PTH. CALCITONIN inhibits osteoclasts, thus decreasing blood Ca2+ level. PARATHYROID HORMONE (PTH) promotes release of Ca2+ from bone extracellular matrix into blood and slows loss of Ca2+ in urine, thus increasing blood Ca2+ level. 3 4 2 5 1 High level of Ca2+ in blood stimulates thyroid gland parafollicular cells to release more CT. CALCITONIN inhibits osteoclasts, thus decreasing blood Ca2+ level. 2 University of Jordan

Adrenal Glands 2 structurally and functionally distinct regions Adrenal cortex Mineralocorticoids affect mineral homeostasis Glucocorticoids affect glucose homeostasis cortisol Androgens have masculinzing effects Dehydroepiandrosterone (DHEA) only important in females Adrenal medulla Modified sympathetic ganglion of autonomic nervous system Intensifies sympathetic responses Epinephrine and norepinephrine University of Jordan

Adrenal Glands University of Jordan

Adrenal Glands Paired organs that cap the kidneys. Each gland consists of an outer cortex and inner medulla. Adrenal medulla: Derived from embryonic neural crest ectoderm (same tissue that produces the sympathetic ganglia). Synthesizes and secretes: Catecholamines (mainly Epi but some NE). University of Jordan

Adrenal Glands (continued) Adrenal cortex: Does not receive neural innervation. Must be stimulated hormonally (ACTH). Consists of 3 zones: Zona glomerulosa. Zona fasciculata. Zona reticularis. Secretes corticosteroids. University of Jordan

Functions of the Adrenal Cortex Zona glomerulosa: Mineralcorticoids (aldosterone): Stimulate kidneys to reabsorb Na+ and secrete K+. Zona fasciculata: Glucocorticoids (cortisol): Inhibit glucose utilization and stimulate gluconeogenesis. It is anti inflammatory (Stabilizes lysosomal membranes) At higher conc. it has mineralocorticoid action Zona reticularis (DHEA): Sex steroids: Supplement sex steroids in males and females University of Jordan

Functions of the Adrenal Cortex (continued) University of Jordan

University of Jordan

Functions of the Adrenal Medulla Innervated by preganglionic sympathetic axons. Increase respiratory rate. Increase HR and cardiac output. Vasoconstrict blood vessels, thus increasing venous return. Stimulate glycogenolysis. Stimulate lipolysis. University of Jordan

Stress and the Adrenal Gland Non-specific response to stress produces the general adaptation syndrome (GAS). Alarm phase: Adrenal glands activated. Stage of resistance: Stage of readjustment. Stage of exhaustion: Sickness and/or death if readjustment is not complete. University of Jordan

University of Jordan

University of Jordan

University of Jordan

Pancreatic Islets Both exocrine and endocrine gland Roughly 99% of cells produce digestive enzymes Pancreatic islets or islets of Langerhans Alpha or A cells secrete glucagon – raises blood sugar Beta or B cells secrete insulin – lowers blood sugar Delta or D cells secrete somatostatin – inhibits both insulin and glucagon F cells secrete pancreatic polypeptide – inhibits somatostatin, gallbladder contraction, and secretion of pancreatic digestive enzymes University of Jordan

Pancreas University of Jordan

Pancreatic Islets (Islets of Langerhans) Alpha cells secrete glucagon. Stimulus is decrease in blood [glucose]. Stimulates glycogenolysis and lipolysis. Stimulates conversion of fatty acids to ketones. Beta cells secrete insulin. Stimulus is increase in blood [glucose]. Promotes entry of glucose into cells. Converts glucose to glycogen and fat. Aids entry of amino acids into cells. University of Jordan

Negative Feedback Regulation of Glucagon and Insulin University of Jordan

Insulin acts on various body cells to: • accelerate facilitated diffusion of glucose into cells • speed conversion of glucose into glycogen (glycogenesis) • increase uptake of amino acids and increase protein synthesis • speed synthesis of fatty acids (lipogenesis) • slow glycogenolysis • slow gluconeogenesis Glucagon acts on hepatocytes (liver cells) to: • convert glycogen into glucose (glycogenolysis) • form glucose from lactic acid and certain amino acids (gluconeogenesis) Glucose released by hepatocytes raises blood glucose level to normal If blood glucose continues to rise, hyperglycemia inhibits release of glucagon Low blood glucose (hypoglycemia) stimulates alpha cells to secrete High blood glucose (hyperglycemia) stimulates beta cells to secrete INSULIN GLUCAGON 1 5 2 3 4 6 Insulin acts on various body cells to: • accelerate facilitated diffusion of glucose into cells • speed conversion of glucose into glycogen (glycogenesis) • increase uptake of amino acids and increase protein synthesis • speed synthesis of fatty acids (lipogenesis) • slow glycogenolysis • slow gluconeogenesis Blood glucose level falls Glucagon acts on hepatocytes (liver cells) to: • convert glycogen into glucose (glycogenolysis) • form glucose from lactic acid and certain amino acids (gluconeogenesis) Glucose released by hepatocytes raises blood glucose level to normal If blood glucose continues to rise, hyperglycemia inhibits release of glucagon Low blood glucose (hypoglycemia) stimulates alpha cells to secrete High blood glucose (hyperglycemia) stimulates beta cells to secrete INSULIN GLUCAGON 1 5 2 3 4 6 7 Insulin acts on various body cells to: • accelerate facilitated diffusion of glucose into cells • speed conversion of glucose into glycogen (glycogenesis) • increase uptake of amino acids and increase protein synthesis • speed synthesis of fatty acids (lipogenesis) • slow glycogenolysis • slow gluconeogenesis If blood glucose continues to fall, hypoglycemia inhibits release of insulin Blood glucose level falls Glucagon acts on hepatocytes (liver cells) to: • convert glycogen into glucose (glycogenolysis) • form glucose from lactic acid and certain amino acids (gluconeogenesis) Glucose released by hepatocytes raises blood glucose level to normal If blood glucose continues to rise, hyperglycemia inhibits release of glucagon Low blood glucose (hypoglycemia) stimulates alpha cells to secrete High blood glucose (hyperglycemia) stimulates beta cells to secrete INSULIN GLUCAGON 1 5 2 3 4 6 7 8 Glucagon acts on hepatocytes (liver cells) to: • convert glycogen into glucose (glycogenolysis) • form glucose from lactic acid and certain amino acids (gluconeogenesis) Glucose released by hepatocytes raises blood glucose level to normal If blood glucose continues to rise, hyperglycemia inhibits release of glucagon Low blood glucose (hypoglycemia) stimulates alpha cells to secrete High blood glucose (hyperglycemia) stimulates beta cells to secrete GLUCAGON 1 5 2 3 4 INSULIN Glucagon acts on hepatocytes (liver cells) to: • convert glycogen into glucose (glycogenolysis) • form glucose from lactic acid and certain amino acids (gluconeogenesis) Glucose released by hepatocytes raises blood glucose level to normal If blood glucose continues to rise, hyperglycemia inhibits release of glucagon Low blood glucose (hypoglycemia) stimulates alpha cells to secrete GLUCAGON 1 2 3 4 Low blood glucose (hypoglycemia) stimulates alpha cells to secrete 1 GLUCAGON Glucagon acts on hepatocytes (liver cells) to: • convert glycogen into glucose (glycogenolysis) • form glucose from lactic acid and certain amino acids (gluconeogenesis) Low blood glucose (hypoglycemia) stimulates alpha cells to secrete GLUCAGON 1 2 Glucagon acts on hepatocytes (liver cells) to: • convert glycogen into glucose (glycogenolysis) • form glucose from lactic acid and certain amino acids (gluconeogenesis) Glucose released by hepatocytes raises blood glucose level to normal Low blood glucose (hypoglycemia) stimulates alpha cells to secrete GLUCAGON 1 2 3 University of Jordan

Ovaries and Testes Gonads – produce gametes and hormones Ovaries produce 2 estrogens (estradiol and estrone) and progesterone With FSH and LH regulate menstrual cycle, maintain pregnancy, prepare mammary glands for lactation, maintain female secondary sex characteristics Inhibin inhibits FSH Relaxin produced during pregnancy Testes produce testosterone – regulates sperm production and maintains male secondary sex characteristics University of Jordan

Pineal Gland Attached to roof of 3rd ventricle of brain at midline Masses of neuroglia and pinealocytes Melatonin – amine hormone derived from serotonin Appears to contribute to setting biological clock More melatonin liberated during darkness than light University of Jordan

Pineal Gland Secretes melatonin: Production stimulated by the suprachiasmatic nucleus (SCN) in hypothalamus. SCN is primary center for circadian rhythms. Light/dark changes required to synchronize. Melatonin secretion increases with darkness and peaks in middle of night. May inhibit GnRH. May function in the onset of puberty (controversial). University of Jordan

Pineal Gland (continued) University of Jordan

Thymus and Other Endocrine Tissues Located behind sternum between the lungs Produces thymosin, thymic humoral factor (THF), thymic factor (TF), and thymopoietin All involved in T cell maturation University of Jordan

Thymus Site of production of T cells (thymus-dependent cells), which are lymphocytes. Lymphocytes are involved in cell-mediated immunity. Secretes hormones that are believed to stimulate T cells after leave thymus. Thymus gland size is large in newborns and children. Regresses after puberty and becomes infiltrated with strands of fibrous tissue. University of Jordan

Gonads and Placenta Gonads (testes and ovaries): Placenta: Secrete sex hormones. Testosterone. Estradiol 17-b. After menopause, produces estrone. Progesterone. Placenta: Secretes large amounts of estriol, progesterone, hCG, hCS. University of Jordan

Prostaglandins Most diverse group of autocrine regulators. Produced in almost every organ. Wide variety of functions. Different prostaglandins may exert antagonistic effects in some tissues. Immune system: Promote inflammatory process. Reproductive system: Play role in ovulation. Digestive system: Inhibit gastric secretion. University of Jordan

Prostaglandins (continued) University of Jordan

Prostaglandins (continued) Respiratory system: May bronchoconstrict or bronchodilate. Circulatory system: Vasoconstrictors or vasodilators. Urinary system: Vasodilation. Inhibitors of prostaglandin synthesis: Non-steroidal anti-inflammatory drugs (NSAIDS). Aspirin, indomethacin, ibuprofen: inhibit COX1. Celecoxib and rofecoxib: inhibit COX2. University of Jordan

The Stress Response Eustress in helpful stress / Distress is harmful Body’s homeostatic mechanisms attempt to counteract stress Stressful conditions can result in stress response or general adaptation syndrome (GAS) 3 stages – initial flight-or-fight, slower resistance reaction, eventually exhaustion Prolonged exposure to cortisol can result in wasting of muscles, suppression of immune system, ulceration of GI tract, and failure of pancreatic beta cells University of Jordan

Stress Response University of Jordan

Thank You University of Jordan