Copyright ©2002 The McGraw-Hill Companies.

1. Copyright ©2002 The McGraw-Hill Companies. Endocrine system Chapter 17 extraído de: Anatomy and Physiology 2nd. edition, Kenneth S. Saladin McGraw-Hill veja mais sobre este assunto em: http://www.biocourse.com/mhhe/bcc/domains/quad/topic.xsp?id=000318

2. Chapter 17 Endocrine System • Hormone • chemical messenger secreted into bloodstream, stimulates response in another tissue or organ • Target cells • have receptors for hormone • Endocrine glands • produce hormones • Endocrine system • includes hormone producing cells in organs such as brain, heart and small intestine

3. Endocrine Organs • Major organs of endocrine system

4. Endocrine vs. Exocrine Glands • Endocrine glands • no ducts, release hormones into tissue fluids, have dense capillary networks to distribute hormones • intracellular effects, alter target cell metabolism • Exocrine glands • ducts carry secretion to body surface or other organ cavity • extracellular effects (food digestion)

5. Comparison of Nervous and Endocrine Systems • Communication and adaptation • electrical impulses and neurotransmitters, adapts quickly to continual stimulation • hormones in blood, adapts slowly (days to weeks) • Speed and persistence of response • reacts quickly (1 - 10 msec), stops quickly • reacts slowly (seconds to days), may continue long after stimulus stops • Area of effect • local, specific effects on target organs • general, widespread effects on many organs

6. Similarities Between Systems • Neuroendocrine cells • neurons that secrete hormones into ECF • Several chemicals function as both neurotransmitters and hormones (norepinephrine) • Systems overlapping effects on same target cells • Systems regulate each other • neurons trigger hormone secretion • hormones stimulate or inhibit neurons

7. Hypothalamus • Shaped like a flattened funnel, forms floor and walls of third ventricle • Regulates primitive functions from water balance to sex drive • Many functions carried out by pituitary gland

8. Pituitary Gland (Hypophysis) • Suspended from hypothalamus by stalk (infundibulum) • Location and size • housed in sella turcica of sphenoid bone • 1.3 cm diameter

9. Embryonic Development of Pituitary

10. Pituitary Gland Anatomy and Hormones of the Neurohypophysis

11. Hypothalamo-Hypophyseal Portal System • Hormones (red box)secreted by anterior pituitary (under control of hypothalamic releasers and inhibitors) Gonadotropin- releasing hormone controls FSH + LH release Thyrotropin- releasing hormone Corticotropin- releasing hormone Prolactin- releasing factor Prolactin- inhibiting factor GH- releasing hormone GH- inhibiting hormone • Hormones secreted by hypothalamus, travel in portal system to anterior pituitary

12. Pituitary Hormones - Anterior Lobe • Tropic hormones target other endocrine glands • gonadotropins target gonads, FSH (follicle stimulating hormone) and LH (luteinizing hormone) • TSH (thyroid stimulating hormone) • ACTH (adrenocorticotropic hormone) • PRL (prolactin) • GH (growth hormone )

13. Anterior Pituitary Hormones • Principle hormones and target organs shown • Axis - refers to way endocrine glands interact

14. Pituitary Hormones - Pars Intermedia • Adult human these cells fuse with anterior lobe • Produce POMC (pro-opiomelanocortin) which is processed into ACTH and endorphins

15. Pituitary Hormones - Posterior Lobe • Stores and releases OT and ADH • OT (oxytocin) and ADH produced in hypothalamus, transported down to posterior lobe by hypothalamo-hypophyseal tract

16. Hormone Actions • FSH • ovaries, stimulates development of eggs and follicles • testes, stimulates production of sperm • LH • females, stimulates ovulation and corpus luteum to secrete progesterone • males, stimulates interstitial cells of testes to secrete testosterone • ACTH • regulates response to stress, effect on adrenal cortex and secretion of glucocorticoids

17. Hormone Actions 2 • PRL • female, milk synthesis • male,  LH sensitivity, thus  testosterone secretion • ADH • targets kidneys to  water retention, reduce urine • also functions as neurotransmitter • Oxytocin • labor contractions, lactation • possible role sperm transport, emotional bonding

18. Growth Hormone • Targets liver to produce somatomedins  mitosis + cellular differentiation for tissue growth • protein synthesis • mRNA translated,  DNA transciption for  mRNA production • enhances amino acid transport into cells,  catabolism • lipid metabolism • stimulates FFA and glycerol release, protein sparing • CHO metabolism • glucose sparing effect- glucose stored as glycogen • Electrolyte balance • promotes Na+, K+, Cl- retention, Ca+2 absorption

19. Growth Hormone 2 • Childhood • bone, cartilage and muscle growth • Adulthood • osteoblastic activity, appositional growth affecting bone thickening and remodeling • Levels of GH • higher during first 2 hours of deep sleep, after high protein meals, after vigorous exercise • lower after high CHO meals • decline with age

20. Control of Pituitary: Hypothalamic and Cerebral • Anterior lobe control - releasing hormones and inhibiting hormones of hypothalamus • Posterior lobe control - neuroendocrine reflexes • hormone release in response to nervous system signals • suckling infant stimulates nerve endings  hypothalamus  posterior lobe  oxytocin  milk ejection • hormone release in response to higher brain centers • milk ejection reflex can be triggered by a baby's cry

21. Control of Pituitary: Feedback from Target Organs • Negative feedback •  target organ hormone levels inhibits release of tropic hormones • Positive feedback • stretching of uterus  OT release, causes stretching of uterus  OT release, until delivery

22. Pituitary Disorders • Hypopituitarism • pituitary dwarfism • childhood  GH • panhypopituitarism • complete cessation of pituitary secretion • causes broad range of disorders • diabetes insipidus •  ADH, 10x normal urine output

23. Pituitary Disorders • Hyperpituitarism • childhood • gigantism • adult • acromegaly - thickening of bones, soft tissues of hands, feet and face

24. Pineal gland Pineal Gland • Peak secretion 1-5 yr. olds, by puberty 75% lower • Produces serotonin by day, converts it to melatonin at night • May regulate timing of puberty in humans • Melatonin  in SAD + PMS,  by phototherapy

25. Thymus • Location: mediastinum, superior to heart • Involution after puberty • Secretes hormones that regulate development and later activation of T-lymphocytes

26. Thyroid Gland Anatomy • Largest endocrine gland • Anterior and lateral sides of trachea • 2 large lobes connected by isthmus

27. Thyroid Gland • Thyroid follicles • filled with colloid and lined with simple cuboidal epith. (follicular cells) that secretes 2 hormones, T3+T4 • Thyroid hormone •  body’s metabolic rate and O2 consumption • calorigenic effect -  heat production •  heart rate and contraction strength •  respiratory rate • Parafollicular cells • produce calcitonin that  blood Ca+2, promotes Ca+2 deposition and bone formation especially in children

28. Thyroid Gland Disorders • Congenital hypothyroidism (TH) • infant suffers abnormal bone development, thickened facial features, low temperature, lethargy, brain damage • Myxedema (adult hypothyroidism, TH) • low metabolic rate, sluggishness, sleepiness, weight gain, constipation, dry skin and hair, cold sensitivity,  blood pressure and tissue swelling • Endemic goiter (goiter = enlarged thyroid gland) • dietary iodine deficiency, no TH, no - feedback,  TSH • Toxic goiter (Graves disease) • antibodies mimic TSH, TH, exophthalmos

29. Parathyroid Glands • PTH •  blood Ca+2 •  absorption •  urinary excretion • bone resorption • Hypoparathyroid • surgical excision • fatal tetany 3-4 days • Hyperparathyroid • tumor; causes soft, fragile and deformed bones,  blood Ca+2, renal calculi

30. Adrenal Gland

31. Adrenal Medulla • Sympathetic ganglion innervated by sympathetic preganglionic fibers • stimulation causes release of (nor-)epinephrine

32. Adrenal Cortex • 3 layers • (outer) zona glomerulosa, (middle) zona fasciculata, (inner) zona reticularis • Corticosteroids • mineralocorticoids (zona glomerulosa) • control electrolyte balance, aldosterone promotes Na+ retention and K + excretion • glucocorticoids (zona fasciculata - response to ACTH) • especially cortisol, stimulates fat + protein catabolism, gluconeogenesis (from a.a.’s + FA’s) and release of fatty acids and glucose into blood to repair damaged tissues • sex steroids (zona reticularis) • androgens, including DHEA (other tissues convert to testosterone) and estrogen (important after menopause)

33. Adrenal Disorders • Pheochromocytoma • tumor of adrenal medulla, with hypersecretion of (nor-)epinephrine • causes  BP,  metabolic rate, hyperglycemia, glycosuria, nervousness, indigestion, sweating • Cushing syndrome (adrenal tumor, excess ACTH) • causes hyperglycemia, hypertension, weakness, edema • muscle, bone loss with fat deposition shoulders + face

34. Adrenogenital Syndrome (AGS) • Androgen hypersecretion causes enlargement of penis or clitoris and premature onset of puberty. • Prenatal AGS in girls can result in masculinized genitals (photo) • AGS in women can result in deep voice, beard, body hair

35. Addison Disease • Hyposecretion of glucocorticoids and mineralocorticoids by adrenal cortex • Hypoglycemia, Na+ and K+ imbalances, dehydration, hypotension, weight loss, weakness • Causes  pituitary ACTH secretion, stimulates melanin synthesis and bronzing of skin

36. Pancreas • Retroperitoneal, inferior and dorsal to stomach

37. Pancreatic Hormones • Mostly exocrine gland with pancreatic islets of endocrine cells that produce: • Insulin (from  cells) • secreted after meal with carbohydrates raises glucose blood levels • stimulates glucose and amino acid uptake • nutrient storage effect (stimulates glycogen, fat and protein synthesis • antagonizes glucagon

38. Pancreatic Hormones 2 • Glucagon (from  cells) • secreted in very low carbohydrate and high protein diet or fasting • stimulates glycogenolysis, fat catabolism (release of FFA’s) and promotes absorption of amino acids for gluconeogenesis • Somatostatin (growth hormone-inhibiting hormone, from delta () cells) • secreted with rise in blood glucose and amino acids after a meal • paracrine secretion- modulates secretion of  +  cells

39. Diabetes Mellitus • Signs and symptoms • polyuria, polydipsia, polyphagia • hyperglycemia, glycosuria, ketonuria • osmotic diuresis : blood glucose levels rise above transport maximum of kidney tubules, glucose remains in urine, osmolarity  and draws water into urine • Type I (IDDM) - 10% • some cases have autoimmune destruction of  cells, diagnosed about age 12 • treated with diet, exercise, monitoring of blood glucose and periodic injections of insulin or insulin pump

40. Diabetes Mellitus 2 • Type II (NIDDM) - 90% • insulin resistance • failure of target cells to respond to insulin • 3 major risk factors are heredity, age (40+) and obesity • treated with weight loss program of diet and exercise, • oral medications improve insulin secretion or target cell sensitivity

41. Pathology of Diabetes • Acute pathology: cells cannot absorb glucose, rely on fat and proteins (weight loss + weakness) • fat catabolism  FFA’s in blood and ketone bodies • ketonuria promotes osmotic diuresis, loss of Na+ + K+ • ketoacidosis occurs as ketones  blood pH • if continued causes dyspnea and eventually diabetic coma • Chronic pathology • chronic hyperglycemia leads to neuropathy and cardiovascular damage • retina and kidneys (common in type I), atherosclerosis leading to heart failure (common in type II), and gangrene

42. Hyperinsulinism • From excess insulin injection or pancreatic islet tumor • Causes hypoglycemia, weakness and hunger • triggers secretion of epinephrine, GH and glucagon • side effects: anxiety, sweating and  HR • Insulin shock • uncorrected hyperinsulinism with disorientation, convulsions or unconsciousness

43. Histology of Ovary

44. Ovary • Granulosa cells: wall of ovarian follicle • produces estradiol, first half of menstrual cycle • Corpus luteum: follicle after ovulation • produces progesterone for 12 days or several weeks with pregnancy • Functions • development of female reproductive system and physique • regulate menstrual cycle, sustain pregnancy • prepare mammary glands for lactation • Both secrete inhibin: suppresses FSH secretion

45. Histology of Testis

46. Testes • Interstitial cells (between seminiferous tubules) • produce testosterone • Functions • development of male reproductive system and physique • sustains sperm production and sex drive • Sustentacular cells • secrete inhibin: suppresses FSH secretion, stabilizes sperm production rates

47. Endocrine Functions of Other Organs • Heart - atrial natriuretic factor •  blood volume +  BP, from  Na+ and H2O loss by kidneys • Kidneys • calcitriol - Ca+2 and phosphate:  absorption,  loss for bone deposition • erythropoietin - stimulates bone marrow to produce RBC’s • Stomach and small intestines - enteric hormones • coordinate digestive motility and secretion

48. Endocrine Functions of Other Organs 2 • Liver • angiotensinogen (a prohormone) • precursor of angiotensin II, a vasoconstrictor • erythropoietin (15%) • somatomedins - mediate action of GH • Placenta • secretes estrogen, progesterone and others • regulate pregnancy, stimulate development of fetus and mammary glands

49. Peptides and glycoproteins • OT, ADH; all releasing and inhibiting hormones of hypothalamus; most of anterior pituitary hormones Hormone Chemistry • Steroids • derived from cholesterol • sex steroids, corticosteroids • Monoamines (biogenic amines) • derived from tyrosine • catecholamines (norepinephrine, epinephrine, dopamine) and thyroid hormones

50. Hormone Transport • Transport proteins (albumins and globulins) • steroids and thyroid hormone are hydrophobic and must bind to transport proteins for transport • bound hormone - hormone attached to transport protein, (half-life hours to weeks, protects from enzymes and kidney filtration) • only unbound hormone can leave capillary to reach target cell (half-life a few minutes)