1. 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 Chapter 17 Endocrine System

2. Endocrine Organs Major organs of endocrine system

3. 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)

4. 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

5. 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

6. 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

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

8. Embryonic Development of Pituitary

9. Pituitary Gland Anatomy and Hormones of the Neurohypophysis

10. 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 Hypothalamo-Hypophyseal Portal System Hormones (red box)secreted by anterior pituitary (under control of hypothalamic releasers and inhibitors) Hormones secreted by hypothalamus, travel in portal system to anterior pituitary

11. 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 ) Pituitary Hormones - Anterior Lobe

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

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

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

15. 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

16. 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 Hormone Actions 2

17. 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 Growth Hormone

18. 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 Growth Hormone 2

19. 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

20. 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

21. 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

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

23. 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 Pineal gland

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

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

26. Thyroid Gland Thyroid follicles – filled with colloid and lined with simple cuboidal epith. (follicular cells) that secretes 2 hormones, T 3 +T 4 –Thyroid hormone  body’s metabolic rate and O 2 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

27. 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

28. 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

29. Adrenal Gland

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

31. 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 oestrogen (important after menopause)

32. 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

33. 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

34. 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

35. Pancreas Retroperitoneal, inferior and dorsal to stomach

36. 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

37. 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

38. 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

39. 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

40. 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

41. 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

42. Histology of Ovary

43. Ovary Granulosa cells: wall of ovarian follicle –produces oestradiol, 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

44. Histology of Testis

45. 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

46. Endocrine Functions of Other Organs Heart - atrial natriuretic factor –  blood volume +  BP, from  Na + and H 2 O 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

47. 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 oestrogen, progesterone and others regulate pregnancy, stimulate development of fetus and mammary glands

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

49. 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)

50. Hormone Transport & Action Steroids and thyroid hormone require transport protein, but easily enter cell Monoamines and peptides transport easily in blood, but cannot enter cell and must bind to receptors

51. Hormone Receptors Located on plasma membrane, mitochondria and other organelles, or in nucleus Usually thousands for given hormone –turn metabolic pathways on or off when hormone binds Exhibit specificity and saturation

52. Steroid Hormones Synthesized from cholesterol

53. Steroid Hormones Hydrophobic, depend on transport proteins, long lasting effects Enter target cells easily, enter nucleus and bind to receptor associated with DNA Receptor has 3 regions –one binds the hormone –one binds to acceptor site on chromatin –one activates DNA transcription leads to synthesis of proteins, alter metabolism of target cells

54. Peptides Synthesis –preprohormone - has leader sequence, guides it to RER which removes leader sequence, now its called a –prohormone - RER transfers it to Golgi complex, may modify it, then packages it for secretion

55. Insulin Synthesis Begins as preproinsulin the leader sequence is removed, chain folds, 3 disulfide bridges form and called Proinsulin, in Golgi C peptide removed leaving Insulin

56. cAMP as Second Messenger 1) Hormone binds activates G protein 2) Activates adenylate cyclase 3) Produces cAMP 4) Activates kinases 5) Activates enzymes 6) Metabolic reactions

57. Hormone Action, Other 2nd & 3rd Messengers

58. Monoamines Synthesized from tyrosine, mostly hydrophilic, activate second messenger systems TH only one made from 2 tyrosine molecules

59. Thyroid Hormone Synthesis (1) I - transported into cell then (2) I - + thyroglobulin released into lumen (3-5 next slide) (6)TSH stimulates pinocytosis, lysosome liberates TH, carried by thyroxine-binding globulin

60. Thyroid Hormone Synthesis

61. Thyroid Hormone Action TH binds to receptors on mitochondria (  metabolic rate), ribosomes and chromatin (  protein synthesis) One protein produced: Na + -K + ATPase generates heat

62. Enzyme Amplification

63. Regulation of Cell Sensitivity to a Hormone

64. Hormone Interactions Most cells sensitive to more than one hormone and exhibit interactive effects Synergistic effects Permissive effects –one hormone enhances response to a second hormone Antagonistic effects

65. Stress and Adaptation Any situation that upsets homeostasis and threatens one’s physical or emotional well-being causes stress Way body reacts to stress called the general adaptation syndrome, occurs in 3 stages –alarm reaction –stage of resistance –stage of exhaustion

66. Alarm Reaction Initial response  epinephrine and norepinephrine levels  HR and  BP  blood glucose levels Sodium and water retention (aldosterone)

67. Stage of Resistance After a few hours, glycogen reserves gone  ACTH and cortisol levels Fat and protein breakdown Gluconeogenesis Depressed immune function Susceptibility to infection and ulcers

68. Stage of Exhaustion Stress that continues until fat reserves are gone Protein breakdown and muscle wasting Loss of glucose homeostasis Hypertension and electrolyte imbalances (loss of K + and H + ) Hypokalemia and alkalosis leads to death

69. Paracrine Secretions Chemical messengers that diffuse short distances and stimulate nearby cells –unlike neurotransmitters not produced in neurons –unlike hormones not transported in blood Eicosanoids –an important family of paracrine secretions

70. Eicosanoids Derived from arachidonic acid –released from plasma membrane, 2 enzymes convert it –lipoxygenase converts arachidonic acid to leukotrienes that mediate allergic and inflammatory reactions –cyclooxygenase converts arachidonic acid to –prostacyclin: produced by blood vessel walls, inhibits blood clotting and vasoconstriction –thromboxanes: produced by blood platelets after injury, they override prostacyclin and stimulate vasoconstriction and clotting –prostaglandins: diverse group including »PGE’s: relaxes smooth muscle in bladder, intestines, bronchioles, uterus and stimulates contraction of blood vessels »PGF’s: opposite effects

71. Eicosanoid Synthesis