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  1. 1. CHAP 18 ENDOCRINE SYSTEM HORMONE – mediator molecules released by glands of the endocrine system ENDOCRINOLOGY – science of the structure and function of the endocrine glands and diagnosis of And treatment of disorders of the endocrine system Exocrine glands – secrete products into ducts that carry the secretions into body cavities, lumen of organs, Outer body surface Endocrine glands – secrete products (hormones) into the interstitial fluid then carried by blood to target Organs Endocrine system – pituitary, thyroid, parathyroid, adrenal, pineal glands - several organs and tissues of the body contain cells that secrete hormones but are not exclusively endocrine glands – hypothalamus, thymus gland, pancreas, ovaries, testes, kidneys, stomach, liver, small intestine, skin, heart, adipose tissue, placenta HORMONE ACTIVITY Hormones - act in very low concentrations - affect only a few cell types - target cell must have the appropriate receptor - 2000 – 100,000 receptors per target cell - if excess hormone is present can get decrease in number of receptors – called down regulation receptors removed by endocytosis in clathrin coated vesicles so the number decreases and cell responsiveness decreases - if hormone amount is deficient number of receptors may increase called up- regulation and makes the target cell more responsive - if block a hormone from interacting with its receptor then hormone cannot perform its normal function RU486 (mifepristone) binds to receptors for progesterone and prevents progesterone fron exerting its normal effects maintain uterine conditions needed for sustaining pregnancy - hormones entering the blood and affecting a target organ are called endocrines - hormones acting locally are called paracrines (acting on neighboring cells) and autocrines (acting on the cells which secrete them) CLASSES OF HORMONES Lipid soluble 1. steroid hormones derived from cholesterol and synthesized on the smooth endoplasmic reticulum 2. thyroid hormones (T3 and T4) iodination and coupling to 2 molecules of tyrosine benzene ring of tyrosine and attached iodines make it very lipid soluble 3. nitric oxide – enzyme is nitric oxide synthase Water soluble 1. amine hormones synthesized by decarboxylating and modifying certain amino acids epinephrine, norepinephrine, dopamine - tyrosine histamine - histidine serotonin and melanin - tryptophan 2. peptide hormones synthesized on RER 3-200 aa long some are glycosylated 3. eicosinoid hormones derived from arachidonic acid a 20 carbon fatty acid prostaglandins and leukotrienes act locally and may act via blood HORMONE TRANSPORT IN BLOOD Water soluble mainly float free in blood and most lipid soluble are attached to transport proteins Small fraction of lipid soluble (0.1 to 10 %) is not bound and can diffuse out and bind to target cell And have effects called free fraction of bound hormone
  2. 2. MECHANISM OF HORMONE ACTION Lipid soluble 1. diffuses through the blood, interstitial fluid, through lipid bilayers of the cell membrane 2. if the cell is a target cell then a receptor awaits inside the cell in nucleus or cytoplasm activated receptor alters gene expression by activating or suppressing specific genes 3. get new mRNA which leaves the nucleus enters the cytoplasm and directs synthesis of new proteins, 4. new proteins alter cell activity Water soluble - CHAP 18 cont. Water soluble hormones Receptors are integral membrane proteins in the plasma membrane hormone is the 1st messenger 2nd messenger is released inside the cell to bring about cellular changes example is cAMP derived from ATP by action of adenylate cyclase 1) water soluble hormone diffuses from the blood through interstitial space and binds to receptor 2) binding activates a G protein which activates adenylate cyclase which converts ATP to cAMP 3) cAMP activates protein kinases (free or bound to membranes) which phosphorylates cellular proteins such as other cellular enzymes causing cellular effects 4) phosphodiesterase inactivates cAMP Hormone Interactions Permissive effects – action of one hormone on a cell requires simultaneous or recent exposure to 2nd Hormone Synergistic effect – 2 hormones working together to exert greater effect Antagonistic effect – one hormone opposes the action of another on target cells Control of Secretion Regulation by: 1) signals from nervous system 2) chemical changes in blood disorders usually involve hyposecretion (low output) or hypersecretion (excess output) HYPOTHALAMUS AND PITUITARY GLAND (HYPOPHYSIS) Hypothalamus – major link between nervous and endocrine systems Receives from other brain regions – limbic system, cerebral cortex, thalamus, reticular activating System painful, stressful, and emotional experiences all cause changes in hypothalamus Secretes at least 9 different hormones and pituitary gland secretes 7 more controlling almost all Aspects of growth, development metabolism, homeostasis Pituitary gland connected to hypothalamus by stalk called infundibulum Pituitary gland has anterior and posterior parts which function differently Anterior Pituitary gland
  3. 3. Release of hormones stimulated by releasing hormones and release is inhibited by inhibiting Hormones the releasing and inhibiting hormones come from the hypothalamus and reach the Anterior pituitary by the hypophyseal portal system of arteries 1) human growth hormone or somatotropin secreted by somatotrophs causes several tissues ( liver, skeletal muscle, cartilage, bone and others) to secrete insulin- like growth factors which cause cells to grow and divide by increasing aa uptake into cells and increasing protein synthesis also decrease rate of protein breakdown and use of aa for ATP production enhance lipolysis Release controlled by growth hormone releasing hormone and growth hormone inhibiting Hormone major regulator of these is blood glucose levels low levels caure increase Release of releasing hormone many other factors contribute to control of release 2) thyroid – stimulating hormone release stimulates production of T3 and T4 from thyroid gland release controlled by thyroid releasing hormone from the hypothalamus 3) FSH AND LH Release causes in females ovulation release stimulates sperm production in males Gonadotropin releasing hormone from the hypothalamus controls release 4) prolactin – milk secretion by mammary glands release controlled by prolactin releasing or inhibiting hormone from the hypothalamus 5) adrenocorticotropic hormone – controls production and secretion of hormones from adrenal cortex controlled by corticotropin releasing hormone stress related stimuli cause release 6) melanocyte stimulating hormone – role in humans not known may cause skin darkening Posterior Pituitary gland Neurohypophysis does not synthesize hormones but stores and releases 2 hormones made in the Hypothalamus 1) oxytocin – targets uterus and breasts contraction of smooth muscle in uterus stimulates milk letdown 2) antidiuretic hormone or vasopressin decreases urine production and water loss from sweat and causes contriction of blood vessels causing increased blood pressure amount released varies with blood osmotic pressure and blood volume high osmotic blood pressure causes increased activity of osmoreceptors which activate secretory cells in hypothalamus to increase release of ADH alcohol causes inhibition of ADH secretion causing increased urine output and dehydration causing thirst and headache of hangover Thyroid Gland Butterfly shaped and inferior to the larynx 2 lateral lobes and isthmus connecting the 2 lobes Microscopic spherical sacs called follicles walls have follicular cells cuboidal cells 2 hormones T3 (triiodothyronine) and T4 (thyroxine) a few cells between follicles called parafollicular cells or C cells produce calcitonin a hormone involved in calcium homeostasis thyroid hormone stored under influence of TSH iodine attached to aa tyrosine synthesizes thyroglobulin a glycoprotein of 5000 aa with more than 100 being tyrosines some tyrosines get iodinated secretes into space called colloid iodine is secreted into the colloid space and gets oxidized by peroxidase in the follicular cell membrane iodine binds to tyrosine residues in thyroglobulin and is stored the protein reenters the cell combines with a lysosome and is digested T3 and T4 are released and diffuse out of the cell enter blood and are bound to thyroxine binding globulin actions – increase basal metabolic rate by increasing use of oxygen to produce ATP by stimulating sodium potassium ATPase pump called calorigenic effect stimulate protein synthesis, increase use of glucose for ATP production, increase lipolysis and enhance cholesterol excretion also important role in maintaining body temp Control of release Need iodine also thyrotropin releasing hormone from hypothalamus and TSH from anterior
  4. 4. Pituitary gland stimulate release v Calcitonin – parafollicular cells of the thyroid gland lowers blood calcium by inhibiting bone Breakdown and stimulating bone uptake of calcium inhibits osteoclasts Parathyroid glands Posterior aspect of thyroid gland 2 superior and 2 inferior cell masses Principal cells – more numerous make parathyroid hormone Oxyphil cells – function unknown Parathyroid hormone – increases activity of osteoclasts to break down bone Increases calcium and magnesium ion reabsorption from kidney PTH causes kidneys to produce calcitrol – active form of vitamin D Increases absorption of calcium, magnesium, phosphates from GI tract ADRENAL GLANDS CHAP 18 end ADRENAL GLANDS One on top of each kidney 2 parts – cortex and medulla produces steroid hormones essential for life complete loss of adrenocortical hormones leads to death from dehydration and electrolyte imbalance unless have replacement therapy medulla produces 2 hormones epinephrine and norepinephrine connective tissue capsule covers the gland Cortex – 3 zones 1) glomerulosa outer zone - mineralocorticoids affect homeostasis of sodium and potassium 2) fasciculata - middle zone - secrete mainly glucocorticoids affect glucose homeostasis 3) reticularis - inner zone - synthesize small amounts of weak androgens a. mineralocorticoids – help to control water and electrolyte homeostasis esp. sodium and potassium 3 different hormones but 95% is aldosterone which acts on kidney tubules to increase reaqbsorp- tion of sodium ion to the blood leads to reabsorption of chloride ion and water molecules promotes secretion of potassium ion and hydrogen ion control of aldosterone - most important is renin-angiotensin pathway stimulated by dehydration, sodium deficiency, or hemorrhage decrease in blood volume leads to decrease in blood pressure detected by juxtaglomerular cells of kidney which secretes renin which converts angiotensinogen to angiotensin I goes to lungs and angiotensin converting enzyme converts I to II II has 2 targets – adrenal cortex which secretes aldosterone which goes to Kidneys - leads to increased sodium reabsorption and water follows Also increases potassium excretion increased water reabsorption leads to increased Blood volume which leads to increased blood pressure Second target of angiotensin II is smooth muscle in arteriole walls which constrict which i Increases blood Pressure Second control mechanism for aldosterone secretion involves potassium ion concentration in Blood increase incpotassium concentration in blood leads to stimulation of aldosterone Secretion by adrenal cortex causing kidneys to excrete more potassium b. Glucocorticoids – regulate metabolism and resistance to stress Include cortisol (hydrocortisone), corticosterone, cortisone 95% is cortisol effects – protein breakdown esp. in muscle - formation of glucose liver converts aa to glucose
  5. 5. - stimulates lipolysis - resistance to stress additional glucose raise blood pressure - anti-inflammatory effects inhibit cells participating in the inflammatory response decrease number of mast cells depress phagocytosis decrease capillary permeability - depress immune responses control via corticotropin releasing hormone from hypothalamus goes to anterior pituitary which secretes ACTH which goes to adrenal cortex c. Androgens - dehydroepiandrosterone contributes to onset of puberty MEDULLA Chromaffin cells get innervation from sympathetic NS Secrete epinephrine and norepinephrine 80% is epinephrine Both mimic effects of sympathetic NS Increase heart rate and force of contraction so increase blood pressure Increase blood to heart, liver, muscles, adipose tissue dilate lungs increase blood levels Of glucose and fatty acids In stress hypothalamic neurons send impulses to sympathetic NS which causes increased Secretion of epi and norepi PANCREAS Endocrine and exocrine 99% are clusters of acini where cells produce digestive enzymes scattered clusters of islets of Langerhans cell types – alpha secrete glucagon beta secrete insulin delta secrete somatostatin F cell secrete pancreatic polypeptide Glucagon and insulin Glucagon increases blood glucose levels insulin lowers blood glucose levels OVARIES and TESTES Ovaries – secrete estrogen and progesterone regulate female reproductive cycle, maintain Pregnancy and prepare mammary glands for lactation - development and maintenance female secondary sex characteristics - secrete inhibin – protein hormone that inhibits FSH - during pregnancy secretes relaxin which increases flexibility of pubic symphysis and helps dilate cervix Testes – secrete testosterone as the primary androgen stimulates sperm production and maintains Male secondary sex characteristics - produce inhibin which inhibits secretion of FSH PINEAL GLAND Pinealocytes secretes melatonin derived from aa serotonin More released in darkness and less in strong light Contributes to biological clock controlled by suprachiasmatic nucleus in hypothalamus Can use to set daily rhythms Seasonal affective disorder – maybe overproduction of melatonin use bright light therapy THYMUS GLAND Hormones are thymosin, thymic humoral factor, thymic factor, thymopoietin Promote proliferation and maturation of T lymphocytes STRESS and THE GENERAL ADAPTATION SYNDROME
  6. 6. Stress response successfully maintains homeostasis GAS does not maintain homeostasis Eustress – helps meet challenges and so is good Distress – harmful Stressor – any stimulus causing stress response Stages of GAS 1. alarm reaction - fight or flight response complex reactions initiated by hypothalamic stimula- tion of sympathetic NS and adrenal medulla increase circulation and promote ATP synthesis nonessential body activities inhibited stress could lead to death but usually short-lived and returns to normal 2. resistance reaction – initiated by hypothalamic releasing hormones and is long-term reaction CRH, TRH and GHRH are involved CRH stimulates pituitary to increase secretion of ACTH which stimulates adrenal cortex to Secrete the mineralocorticoid aldosterone which conserves sodium and eliminates hydrogen Ion get no lower blood pH but get water retention leads to increased blood volume Leads to increased blood pressure ACTH leads adrenal cortex to secrete glucocorticoids Get all those effects GHRH stimulates anterior pituitary to secrete growth hormone which causes breakdown of Triglycerides and conversion of glycogen to glucose TRH leads to anterior pituitary to secrete TSH which causes thyroid to secrete T3 and T4 Which leads to increased use of glucose to make ATP Can return to normal 3. exhaustion – resistance stage use many body resources so cannot be maintained prolonged exposure to high levels of cortisol causes muscle wasting, immune system suppression, GI tract ulcers, failure of pancreatic beta cells Stress and Disease Many diseases have a stress component Interlukin – 1 a cytokine from macrophages links stress and immunity