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Chapter 17 The endocrine system overview hypothalamus – pituitary other glands hormone actions stress 4 ways for cells to communicate gaps – neurotransmission – paracrine – hormones endocrine (blood) vs exocrine (ducts, extracellular) endocrine = intracellular – fenestrated capillaries – seconds to days for a response – affect may last for days or longer – persistent with no accommodation – narrow or widespread affects – chemical communication – some both endocrine and neuroendocrine hypothalamus and pituitary hypothalamus regulates anterior pituitary - by secreting releasing factors - which enter primary capillaries - which travel down venules - and diffuse out of the secondary capillaries – and are picked up by specific pituitary cells – ant pit derived from cells from pharynx posterior pituitary (neurohypophysis) hormones are made in hypothalamic neurons - move down nerve fibers - and are stored in nerve endings in the posterior pituitary - until nerve signal from hypothalamus - trigger release from posterior pituitary – post pit derived from nervous tissue (brain cells) anterior pituitary hormones FSH - follicle stimulating hormone, ovary, estrogen, follicle, testis, sperm production LH - luteinizing hormone, ovulation, corpus lutein makes progesterone, testis makes testosterone TSH – thyroid stimulating hormone, T3, T4, many functions on metabolism, growth, repair, ACTH – adrenocorticotropic hormone, glucocorticoids(cortisol) stress, metabolism, PRL – prolactin, stimulates milk secretion after birth GH – growth hormone, most numerous of AP cells (1000X), mitosis, cell differentiation, growth, repair, metabolism, (hypothalamic pituitary thyroid axis) posterior Pituitary Hormones ADH - anti diuretic hormone, water retention, urine , prevents dehydration, also acts as a neurotransmitter called AVP or arginine vasopressin which constricts blood vessels at pathological levels oxytocin - ↑in both sexes during sexual arousal and orgasm, results in emotional bonding, labor contractions↑, milk flow↑, bonding to newborn↑ control of pituitary secretions info coming into brain - integrated and non integrated info to hypothalamus – hypothalamus has centers for stretch receptors of blood vessels and heart, suckling, osmoreceptors, temperature, stress, blood volume, and more this information is used to regulate and modulate many involuntary functions by stimulation and feedback both positive and negative growth hormone - widespread effects on cartilage, bone, muscle, fat, protein, sugars, metabolism, repair, growth, electrolytes IGF1 (insulin like growth factor 1), IGF2, and somatomedins IGF-1 is a primary mediator of the effects of growth hormone(GH). Growth hormone is made in the anterior pituitary gland, is released into the blood stream, and then stimulates the liver to produce IGF-1. IGF-1 then stimulates systemic body growth, and has growth-promoting effects on almost every cell in the body, especially skeletal muscle, cartilage, bone, liver, kidney, nerves, skin, hematopoietic cell, and lungs. In addition to the insulin-like effects, IGF-1 can also regulate cell growth and development, especially in nerve cells, as well as cellular DNA synthesis. Somatomedins are produced, predominantly by the liver, when growth hormones act on target tissue. Somatomedins inhibit the release of growth hormones by acting directly on anterior pituitary and by stimulating the secretion of somatostatin from the hypothalamus. Somatomedins are a group of hormones that promote cell growth and division in response to stimulation by growth hormone (GH) also known as somatotropin (STH). Somatomedins have similar biological effects to somatotropin. In addition to their actions that stimulate growth, somatomedins also stimulate production of somatostatin, which suppresses growth hormone release. Thus, levels of somatomedins are controlled via negative feedback through the intermediates of somatostatin and growth hormone. Somatomedins are produced in many tissues and have autocrine and paracrine actions in addition to their endocrine action. The liver is thought to be the predominant source of circulating somatomedins. IGFs have a half life of almost a full day and produce most of the functions associated with growth hormone proteins - boosts translation and transcription, stimulates anabolism and inhibits catabolism lipids - stimulates catabolism, protein sparing sugars - glucose sparing, gluconeogenesis by liver electrolytes - Na↑, K↑, Cl↑, Ca absorption↑ sleep - GH↑ 2X or more after 2 hours of sleep, 90 minute cycle of release, trauma and stress cause GH↑, hypoglycemia ↑, high protein meals GH↑, high carbohydrate meals GH↓, GH levels = 20 ngm/ml sleep, 30 exercise, 6 adolescence, 1.5 at 65, half life up to 20 minutes pineal gland at roof of 3rd ventricle – large and active in children 1 – 5, secretions decline greatly after puberty, involved with circadian rhythms, serotonin converted into melatonin (sleep), secretions fluctuate with light cycles and seasons, regulates breeding and fertility cycles in lower vertebrates and probably in mammals, pineal pathology = precocious puberty, 3rd eye to neuroendocrine transducer the thymus endocrine, lymphatic, & immune system large in fetus, grows until 5 – 6 years old, shrinks from childhood to adult and then again in 60+ years T cell production, thymopoietin, thymosin, thymulin stimulates development of other lymphatic organs the thyroid gland largest purely endocrine gland in adults very vascular, high metabolic rate TRF – TSH – follicles + lumen + colloid – T4 thyroxine 90% – T3 triiodothyronine 10% oxygen use ↑, heat production↑, calorigenic effect, respiration↑, heart rate↑, heart strength of beat↑, appetite↑, alertness↑, reflexes↑, GH secretion↑, growth↑, CHO, lipid, protein catabolism↑, thyroid has non T4 and T3 cells called C cells (parafollicular cells) as Ca↑ - calcitonin secreted – which inhibits parathyroid glands and osteoblast activity important in children not in adults unless pathological parathyroid Glands 4 nodules on the posterior surface of the thyroid secretes PTH parathyroid hormone as a response to lower calcium levels 1% drop in calcium = 100% increase in PTH PTH - osteoclasts↑( Ca & PO4 ↑ in BV) - kidney reabsorbs calcium - calcitriol↑ - collagen synthesis decreases adrenal glands – suprarenals large in newborns and shrinks by 50% by age of 5 cortex 80-90% medulla 10-20%(sym) affects minerals, sugars, electrolytes, immunity, stress, reflexes, energy, healing adrenal medulla – endocrine & sympathetic ganglion - preganglion nf - chromaffin cells(post ganglion nf) - has no dendrites and no axons - releases products to blood vessels (neuroendocrine function) - chromaffins release catecholamines (75% epinepherine, 25% norepinephrine, trace of dopamine - prepares body for physical action, alertness↑, glucose sparing, fatty acid catabolism↑, lactate metabolism↑, insulin↓, heart rate and strength↑, digestion & urine↓, metabolism↑, glycogenolysis↑, gluconeogenesis↑ adrenal cortex - 25+ corticosteroids from cholesterol 5 important steroids as mineral, gluco and sex steroids zona glomerulosa = mineralocorticoids zona fasciculate = spongiocytes, glucocorticoids, androgens zona reticularis = glucocorticoids and androgens aldosterone – kidney – Na in↑, K out↑, H2O in↑ cortisol – hydrocortisone – fat & protein catabolism↑, gluconeogenesis↑, anti inflamitory androgens – DHEA becomes testosterone & dihydrotestosterone, male fetus↑, in puberty pubic & axillary hair & scent glands, libido↑, skeleton growth↑ estradiol – promotes skeletal growth & adult bone mass & secondary sex characters, menstrual cycle, pregnancy, & lactation estrogen – only source past menopause, the pancreas – exocrine & endocrine 1 – 2 million islets of Lamgherhans 20% alpha cells, 70% beta, 5% delta alpha cells = glucagon, glucose release, fat catabolism, AA reabsorb beta cells = insulin, absorb all nutrients, glycogen, fat, AA↑, brain, liver, kidneys, & RBC use glucose without need for insulin, delta cells = somatostatin, GH inhibition, stomach acid inhibition PP & G cells = unknown functions the gonads – exocrine and endocrine produce hormones, eggs, and sperm ovaries = estradiol, progesterone, inhibin theca cells = of follicle, androgens then converted to estrogens corpus luteum = progesterone testis = seminiferous tubules make testosterone, sertoli cells = inhibin decreases FSH which reduces sperm interstitial cells = testosterone & other steroids other endocrines skin = cholesterol –liver to cholecaciferol - kidney to calcitriol liver = IGF, hepcidin(iron), erythropoietin[EPO](15%), angiotensinogen(BP), kidneys = calcitriol(D3), renin(RAA, BV constriction), EPO(85%) heart = natriuretic peptides, Na out↑, urine vol↑, BP↓ adipose = leptin↓ appetite↑, leptin↑ appetite↓,affects hypothalamus and active during onset of puberty osseous = osteoblasts – osteocalcin – beta cells #↑, insulin↑, inhibits weight gain and development of type 2 diabetes placenta = estrogen, progesterone, and more during fetal development, and mammary growth during pregnancy stomach/small & large intestines = enteroendocrine cells – more than 10 hormones – cholecystokinin (CCK) – release of bile in response to fat in food – anti appeite affect on brain – gastrin from stomach + food = HCl secretion – ghrelin from stomach + empty stomach = hunger – peptide YY(PPY) from small & large intestine signals fullness hormone chemistry steroids, monoamines, peptides, protein bound steroids - from cholesterol (sex steroids, hydrophobic) monoamines – epi, norepi, dopamine, melatonin, T4, T3 peptides-oxytocin,ADH(9AA), many 92AA base+variable beta chain synthesis – 4 ring steroid backbone + different functional groups peptides in active and inactive form, monoamines from tryptophan & others from tyrosine transport – made, released to blood, bound(long lasting) or free receptors – target receptors are proteins or glycoproteins, specific and saturation - - steroids and T4 and T3 pass into cell and initiate 2nd messengers - - cAMP, IP3, diacylglycerol(DAG) initiate cytoplasmic transduction leading to metabolic events amplification - cascade effect, 1-100-10000-1000000, cell sensitivity - up or down with regulation=more or less receptors hormone interactions synergistic (2 + 2 = 8) permissive (increases response speed or magnitude of a 2nd) antagonistic (inhibits speed or magnitude of a 2nd) clearance – broken down when not needed, usually by liver or kidney or local enzymes at target cell metabolic clearance rate = half life rate of destruction stress and adaptation stress is anything which upsets homeostasis and threatens physical or emotional well being can be excess happiness, sadness, grief, despair, etc. stress response (general adaptive syndrome) involves epi and norepi leading to an alarm reaction, resistance to fatigue and homeostatic exhaustion possibly death alarm = norepi from sym & epi from adrenal medulla=flight or flight glycogen catabolism,angiotensin,aldosterone,BP,Na in,H2O in, all↑ resistance = glucose gone, need for alternate fuels, cortisol↑, fat & protein catabolism↑, gluconeogenesis↑, glucose sparing, long term = immunity↓, healing↓, sex hormones↓, body running down exhaustion = no more fat and glycogen, no body chemicals for fuel, only protein left, now in pathology, H2O in, BP, Na in, K out, all ↑, body going into hypokalemia and alkalosis causing nerve and muscle pathology eicosanoids (paracrine signaling) - stimulates nearby cells or same cells - histamines releas by mast cells next to BV & act on BV muscles - nitrous oxide released by BV cells and act on BV cells- vasodilator - catecholamines from adrenal medulla diffuse onto adrenal cortex derived from PUFA (poly unsaturated fatty acid) arachidonic acid cyclooxygenases convert acid to 3 eicosanoids prostacyclins - BV cells, inhibits blood clotting & vasoconstriction thromboxanes-from platelets, stimulate vasoconstriction & clotting prostaglandins – many kinds, affect smooth muscle, inflammation, plus reproduction, kidneys, respiration, GI, NS, endocrines anti inflammatory drugs – inhibit production of eicosanoids SAIDS – steroidal anti inflammatory drugs NSAIDS – non steroidal anti inflammatory drugs COX inhibitors – new class of medicines, new ones arriving each year – stop the conversion of arachidonic acid to eicosanoids – many side effects aspirin does many things – inhibits prostaglandin and thromboxane synthesis