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The Endocrine System Chapter 17


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The Endocrine System Chapter 17

  1. 1. The Endocrine System Chapter 17
  2. 2. Endocrine System <ul><li>Overview </li></ul><ul><ul><li>Endocrinology (endo = into crin = secrete) </li></ul></ul><ul><ul><li>Function </li></ul></ul><ul><ul><li>Hormone </li></ul></ul>FYI “ A whopping increase of 165% in newly diagnosed Type 2 diabetes is expected by the year 2050. Among ethnic groups, the biggest increase is expected among black men (363%), with black women expected to see the second highest increase (217%).” From Live a Little, Laugh a Lot by Barb Bancroft
  3. 3. Overview of Cell Communications <ul><li>Mechanisms </li></ul><ul><ul><li>gap junctions </li></ul></ul><ul><ul><ul><li>pores in cell membrane </li></ul></ul></ul><ul><ul><ul><li>Direct cell to cell </li></ul></ul></ul><ul><ul><li>neurotransmitters </li></ul></ul><ul><ul><ul><li>synapse </li></ul></ul></ul><ul><ul><li>paracrine (local) hormones </li></ul></ul><ul><ul><ul><li>secreted into tissue fluids affect nearby cells </li></ul></ul></ul><ul><ul><ul><li>interferon </li></ul></ul></ul><ul><ul><li>hormones </li></ul></ul>
  4. 4. Endocrine vs. Exocrine Glands <ul><li>Exocrine glands </li></ul><ul><ul><li>ducts carry secretion to a surface </li></ul></ul><ul><ul><li>extracellular effects (food digestion) </li></ul></ul><ul><li>Endocrine glands </li></ul><ul><ul><li>no ducts, release hormones into tissue fluids, capillary networks distribute hormones </li></ul></ul><ul><ul><li>intracellular effects, alter target cell metabolism </li></ul></ul>
  5. 5. <ul><li>Hormone </li></ul><ul><ul><li>chemical messenger stimulates response in other tissues or organs </li></ul></ul><ul><li>Target cells </li></ul><ul><ul><li>Have hormone receptors </li></ul></ul><ul><li>Endocrine glands </li></ul><ul><ul><li>produce hormones </li></ul></ul><ul><li>Endocrine system </li></ul><ul><ul><li>endocrine organs (thyroid, pineal, etc) </li></ul></ul><ul><ul><li>hormone producing cells in organs (brain, heart and small intestine) </li></ul></ul>Endocrine System Components
  6. 6. Nervous vs. Endocrine Systems
  7. 7. Nervous and Endocrine Systems <ul><li>Some chemicals are both hormones and neurotransmitters </li></ul><ul><ul><li>NE, cholecystokinin, thyrotropin-releasing hormone, dopamine and ADH </li></ul></ul><ul><li>Some hormones secreted by neuroendocrine cells (neurons) </li></ul><ul><ul><li>oxytocin and catecholamines </li></ul></ul><ul><li>Systems regulate each other </li></ul><ul><ul><li>neurons trigger hormone secretion </li></ul></ul><ul><ul><li>hormones stimulate or inhibit neurons </li></ul></ul>
  8. 8. Nomenclature
  9. 9. Endocrine Organs <ul><li>Major organs </li></ul>
  10. 10. Hypothalamus <ul><li>Floor and walls of third ventricle </li></ul><ul><li>Regulates functions from water balance to sex drive </li></ul><ul><li>Many functions carried out by pituitary gland </li></ul>
  11. 11. Hypothalamic Hormones
  12. 12. Pituitary Gland (Hypophysis) <ul><li>Location and size </li></ul><ul><ul><li>Suspended from hypothalamus by stalk (infundibulum) </li></ul></ul><ul><ul><li>housed in sella turcica of sphenoid bone </li></ul></ul><ul><ul><li>1.3 cm diameter </li></ul></ul><ul><li>Adenohypophysis (anterior pituitary) </li></ul><ul><li>Neurohypophysis </li></ul>
  13. 13. Secreted Hormones and the Portal System <ul><li>Hormones travel in portal system from hypothalamus to anterior pituitary </li></ul>
  14. 14. <ul><li>PRL (prolactin) </li></ul><ul><li>GH (growth hormone) </li></ul><ul><li>Tropic hormones target other glands </li></ul><ul><ul><li>gonadotropins target gonads </li></ul></ul><ul><ul><ul><li>FSH (follicle stimulating hormone)  eggs and sperm </li></ul></ul></ul><ul><ul><ul><li>LH (luteinizing hormone) </li></ul></ul></ul><ul><ul><ul><ul><li>ovulation; corpus luteum  estrogen, progesterone </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Interstitial cells  testosterone </li></ul></ul></ul></ul><ul><ul><li>TSH (thyroid stimulating hormone)  TH, gland growth </li></ul></ul><ul><ul><li>ACTH (adrenocorticotropic hormone) </li></ul></ul>Pituitary Hormones Anterior Lobe
  15. 15. <ul><li>ACTH or corticotropin (secreted by corticotropes) </li></ul><ul><ul><li>regulates response to stress, stimulates adrenal cortex </li></ul></ul><ul><ul><ul><li>corticosteroids regulate glucose, fat and protein metabolism </li></ul></ul></ul><ul><li>PRL (secreted by lactotropes) </li></ul><ul><ul><li>female - milk synthesis after delivery </li></ul></ul><ul><ul><li>male -  LH sensitivity, thus  testosterone secretion </li></ul></ul>Hormone Actions: Anterior Lobe
  16. 16. <ul><li>Promotes tissue growth (bone, cartilage and muscle growth) </li></ul><ul><ul><li>mitosis & cellular differentiation </li></ul></ul><ul><ul><li>stimulates liver to produce IGF-I (insulin like growth factors/somatomedins) and II </li></ul></ul><ul><ul><ul><li>protein synthesis </li></ul></ul></ul><ul><ul><ul><ul><li> DNA transciption,  mRNA,  proteins </li></ul></ul></ul></ul><ul><ul><ul><ul><li> amino acid transport into cells,  protein catabolism </li></ul></ul></ul></ul><ul><ul><ul><li>lipid metabolism </li></ul></ul></ul><ul><ul><ul><ul><li>stimulates FFA and glycerol release from adipocytes, protein sparing </li></ul></ul></ul></ul><ul><ul><ul><li>CHO metabolism </li></ul></ul></ul><ul><ul><ul><ul><li>glucose sparing effect = less glucose used for energy </li></ul></ul></ul></ul><ul><ul><ul><li>Electrolyte balance </li></ul></ul></ul><ul><ul><ul><ul><li>promotes Na + , K + , Cl - retention, Ca 2+ absorption </li></ul></ul></ul></ul>Growth Hormone (Somatotropin)
  17. 17. <ul><li>Childhood and adolescence </li></ul><ul><ul><li>bone, cartilage and muscle growth </li></ul></ul><ul><ul><li>Stimulates growth at epiphyseal plates </li></ul></ul><ul><li>Adulthood </li></ul><ul><ul><li>increase osteoblastic activity affects bone remodeling </li></ul></ul><ul><ul><li>concentration decreases with age </li></ul></ul><ul><li>Levels of GH (daily fluctuations) </li></ul><ul><ul><li> during deep sleep, after high protein meals, after vigorous exercise </li></ul></ul><ul><ul><li>lower after high CHO meals </li></ul></ul>Growth Hormone and Aging
  18. 18. Hormone Actions: Posterior Lobe <ul><ul><li>Produced in hypothalamus </li></ul></ul><ul><ul><li>transported to and stored in posterior lobe </li></ul></ul><ul><li>ADH (vasopressin) </li></ul><ul><ul><li>targets kidneys </li></ul></ul><ul><ul><ul><li> water retention, reduce urine </li></ul></ul></ul><ul><ul><li>also functions as a brain neurotransmitter </li></ul></ul><ul><li>Oxytocin </li></ul><ul><ul><li>labor contractions, lactation </li></ul></ul><ul><ul><li>possible role in </li></ul></ul><ul><ul><ul><li>sperm transport </li></ul></ul></ul><ul><ul><ul><li>emotional bonding </li></ul></ul></ul>
  19. 19. Control of Pituitary: Feedback from Target Organs <ul><li>Negative feedback </li></ul><ul><ul><li> target organ hormone levels inhibits release of tropic hormones </li></ul></ul><ul><li>Positive feedback </li></ul><ul><ul><li>stretching of uterus  OT release, causes more stretching of uterus, until delivery </li></ul></ul>
  20. 20. Endocrine Disorders <ul><li>Hormone concentration and target cell sensitivity </li></ul><ul><li>Hyposecretion – inadequate hormone release </li></ul><ul><ul><li>tumor or lesion destroys gland </li></ul></ul><ul><ul><ul><li>head trauma affects pituitary gland’s ability to secrete ADH </li></ul></ul></ul><ul><ul><ul><ul><li>diabetes insipidus = chronic polyuria </li></ul></ul></ul></ul><ul><li>Hypersecretion – excessive hormone release </li></ul><ul><ul><li>tumors or autoimmune disorder </li></ul></ul><ul><ul><ul><li>toxic goiter (graves disease) – antibodies mimic effect of TSH on the thyroid </li></ul></ul></ul>
  21. 21. Pituitary Disorders <ul><li>Hypersecretion of growth hormones </li></ul><ul><ul><li>Acromegaly </li></ul></ul><ul><ul><ul><li>middle-aged adults    </li></ul></ul></ul><ul><ul><ul><li>abnormal growth of the hands/feet   </li></ul></ul></ul><ul><ul><ul><li>  bone changes alter facial features including the spacing of teeth    </li></ul></ul></ul><ul><ul><ul><li>arthritis    </li></ul></ul></ul><ul><ul><ul><li>thick, coarse, oily skin; skin tags; enlarged lips, nose and tongue;    </li></ul></ul></ul><ul><ul><ul><li>deepening of the voice due to enlarged sinuses and vocal cords; snoring due to upper airway obstruction;    </li></ul></ul></ul>
  22. 22. <ul><ul><ul><li>excessive sweating and skin odor; fatigue and weakness; headaches; impaired vision;    </li></ul></ul></ul><ul><ul><ul><li>enlargement of body organs, including the liver, spleen, kidneys and heart. </li></ul></ul></ul><ul><ul><li>thickening of the bones and soft tissues </li></ul></ul><ul><ul><li>problems in childhood or adolescence </li></ul></ul><ul><ul><ul><li>gigantism = oversecretion; dwarfism = hyposecretion </li></ul></ul></ul>
  23. 23. Pineal Gland <ul><li>Peak secretion ages 1-5; by puberty 75% lower </li></ul><ul><li>May regulate timing of puberty in humans </li></ul><ul><li>Produces serotonin by day, converts it to melatonin at night </li></ul><ul><li>Melatonin  in SAD + PMS;  by phototherapy </li></ul><ul><ul><li>depression, sleepiness, irritability and carbohydrate craving </li></ul></ul>“ The pineal gland was called the &quot;third eye&quot; by ancient people. It was thought to have mystical powers. This may be why the French philosopher Descartes decided that the pineal gland was the seat of the human soul, the location of what we call the mind. Melatonin is released in the dark, during sleep. Melatonin has been shown to inhibit the growth and metastasis of some tumors in experimental animals, and may therefore play a role in cancer inhibition. Removal of the pineal gland and/or reduction in melatonin output have been implicated in the increased incidence of breast cancer in laboratory animals. Patients who have breast cancer have lower levels of melatonin in the blood. The hormone has also been shown to be protective against genetic damage, and it has a stimulatory effect on the immune system. “
  24. 24. Thymus <ul><li>Location: mediastinum, superior to heart </li></ul><ul><li>Involution after puberty </li></ul><ul><li>Hormones regulate development and later activation of T-lymphocytes </li></ul><ul><ul><li>thymopoietin and thymosins </li></ul></ul>
  25. 25. Thyroid Gland Anatomy <ul><li>Largest endocrine gland; high rate of blood flow </li></ul><ul><li>Anterior and lateral sides of trachea </li></ul><ul><ul><li>two large lobes connected by isthmus </li></ul></ul><ul><li>Thyroid follicles </li></ul><ul><ul><li>filled with colloid and lined with simple cuboidal epithelial (follicular cells) that secretes two hormones, T 3 and T 4 </li></ul></ul>
  26. 26. Thyroid Gland <ul><li>Thyroid hormone </li></ul><ul><ul><li> body’s metabolic rate and O 2 consumption </li></ul></ul><ul><ul><li>calorigenic effect -  heat production </li></ul></ul><ul><ul><li> heart rate and contraction strength </li></ul></ul><ul><ul><li> respiratory rate </li></ul></ul><ul><ul><li>stimulates appetite and breakdown CHO, lipids and proteins </li></ul></ul><ul><ul><li> alertness, bone growth/remodeling </li></ul></ul><ul><li>C (calcitonin or parafollicular) cells </li></ul><ul><ul><li>produce calcitonin  blood Ca 2+ , promotes Ca 2+ deposition and bone formation especially in children </li></ul></ul>
  27. 27. Thyroid Gland Disorders <ul><li>Congenital hypothyroidism (  TH) </li></ul><ul><ul><li>abnormal bone development, thickened facial features, low temperature, lethargy, brain damage </li></ul></ul><ul><li>Myxedema (adult hypothyroidism,  TH) </li></ul><ul><ul><li>low metabolic rate, sluggishness, sleepiness, weight gain, constipation, dry skin and hair, cold sensitivity,  blood pressure and tissue swelling </li></ul></ul><ul><li>Endemic goiter (goiter = enlarged thyroid gland) </li></ul><ul><ul><li>iodine deficiency, no TH, no - feedback,  TSH </li></ul></ul><ul><li>Toxic goiter (Graves disease) </li></ul><ul><ul><li>antibodies mimic TSH,  TH, exophthalmos </li></ul></ul>Nodular pretibial myxedema
  28. 28. Parathyroid Glands <ul><li>PTH release </li></ul><ul><ul><li> blood Ca 2+ levels </li></ul></ul><ul><ul><li>promotes synthesis of calcitriol </li></ul></ul><ul><ul><ul><li> absorption of Ca 2+ </li></ul></ul></ul><ul><ul><ul><li> urinary excretion </li></ul></ul></ul><ul><ul><ul><li> bone resorption </li></ul></ul></ul>
  29. 29. Parathyroid Disorders <ul><li>Hypoparathyroid </li></ul><ul><ul><li>surgical excision during thyroid surgery </li></ul></ul><ul><ul><li>fatal tetany 3-4 days </li></ul></ul><ul><li>Hyperparathyroid = excess PTH secretion </li></ul><ul><ul><li>tumor in gland </li></ul></ul><ul><ul><li>causes soft, fragile and deformed bones </li></ul></ul><ul><ul><li> blood Ca 2+ </li></ul></ul><ul><ul><li>renal calculi </li></ul></ul>
  30. 30. Adrenal Medulla <ul><li>Modified neurons called chromaffin cells </li></ul><ul><ul><li>releases catecholamines (epinephrine, NE) </li></ul></ul><ul><li>Long lasting hormonal effect </li></ul><ul><ul><li> alertness, anxiety, or fear </li></ul></ul><ul><ul><li> BP, heart rate and air flow </li></ul></ul><ul><ul><li>raises metabolic rate </li></ul></ul><ul><ul><ul><li>inhibits insulin secretion </li></ul></ul></ul><ul><ul><ul><li>stimulates gluconeogenesis and glycogenolysis </li></ul></ul></ul><ul><li>Stress causes medullary cells to stimulate cortex </li></ul>
  31. 31. Adrenal Cortex <ul><li>Layers </li></ul><ul><ul><li>zona glomerulosa (outer) </li></ul></ul><ul><ul><li>zona fasciculata (middle) </li></ul></ul><ul><ul><li>zona reticularis (inner) </li></ul></ul>
  32. 32. Adrenal Cortex <ul><li>Corticosteroids </li></ul><ul><ul><li>mineralocorticoids (zona glomerulosa) </li></ul></ul><ul><ul><ul><li>electrolyte balance, aldosterone  Na + retention & K + excretion </li></ul></ul></ul><ul><ul><li>glucocorticoids (zona fasciculata) </li></ul></ul><ul><ul><ul><li>especially cortisol,  fat and protein catabolism, gluconeogenesis (from a.a.’s and FA’s) and releases FAs and glucose into blood </li></ul></ul></ul><ul><ul><ul><li>anti-inflammatory effect becomes immune suppression with long-term use </li></ul></ul></ul><ul><ul><li>sex steroids (zona reticularis) </li></ul></ul><ul><ul><ul><li>androgen (including DHEA) and estrogen (important after menopause) </li></ul></ul></ul>
  33. 33. Adrenal Disorders <ul><li>Cushing syndrome - excess cortical secretion </li></ul><ul><ul><li>hyperglycemia, hypertension, weakness, edema </li></ul></ul><ul><ul><li>Muscle/bone loss occurs with protein catabolism </li></ul></ul><ul><ul><li>buffalo hump and moon face = fat deposition between shoulders or in face </li></ul></ul><ul><li>Adrenogenital syndrome (AGS) </li></ul><ul><ul><li>adrenal androgen hypersecretion; accompanies Cushing </li></ul></ul><ul><ul><li>enlargement of external sexual organs in children and early onset of puberty </li></ul></ul><ul><ul><li>masculinizing effects on women (deeper voice and beard growth) </li></ul></ul>
  34. 34. Pancreas <ul><li>Location - Retroperitoneal, inferior and dorsal to stomach </li></ul><ul><li>Exocrine – digestive enzymes </li></ul><ul><li>Endocrine </li></ul><ul><ul><li>1-2 million islets produce hormones </li></ul></ul><ul><ul><li>Insulin (from  cells) </li></ul></ul><ul><ul><ul><li>secreted after CHO meal  glucose blood levels </li></ul></ul></ul><ul><ul><ul><li>stimulates glucose and amino acid uptake </li></ul></ul></ul><ul><ul><ul><li>nutrient storage effect (stimulates glycogen, fat and protein synthesis) </li></ul></ul></ul>
  35. 35. Pancreatic Hormones <ul><li>Glucagon (from  cells) </li></ul><ul><ul><li>secreted in very low carbohydrate and high protein diet or fasting </li></ul></ul><ul><ul><li>stimulates glycogenolysis, fat catabolism and absorption of AAs for gluconeogenesis </li></ul></ul><ul><li>Somatostatin (from delta (  ) cells) </li></ul><ul><ul><li>secreted with  in blood glucose and AAs after a meal </li></ul></ul><ul><ul><li>paracrine secretion = inhibits secretion of insulin, glucagon by  and  cells </li></ul></ul>
  36. 36. Pancreatic Hormones <ul><li>Hyperglycemic hormones raise blood glucose </li></ul><ul><ul><li>GH, epinephrine, NE, cortisol and corticosterone </li></ul></ul><ul><li>Hypoglycemic hormones lower blood glucose </li></ul><ul><ul><li>insulin </li></ul></ul>
  37. 37. Diabetes Mellitus <ul><li>Signs and symptoms of hyposecretion of insulin </li></ul><ul><ul><li>polyuria, polydipsia, polyphagia </li></ul></ul><ul><ul><li>hyperglycemia, glycosuria, ketonuria </li></ul></ul><ul><ul><li>osmotic diuresis </li></ul></ul><ul><ul><ul><li>blood glucose levels rise above transport maximum of kidney tubules, glucose remains in urine (ketones also present) </li></ul></ul></ul><ul><ul><ul><li>increased osmolarity draws water into urine </li></ul></ul></ul>
  38. 38. Types of Diabetes Mellitus <ul><li>Type I (IDDM) - 10% of cases </li></ul><ul><ul><li>autoimmune destruction of  cells, diagnosed ~ 12 </li></ul></ul><ul><ul><li>treat with diet, exercise, monitoring of blood glucose and insulin injections </li></ul></ul><ul><li>Type II (NIDDM) - 90% </li></ul><ul><ul><li>insulin resistance </li></ul></ul><ul><ul><ul><li>failure of target cells to respond to insulin </li></ul></ul></ul><ul><ul><li>risk factors: heredity, age (40+) and obesity </li></ul></ul><ul><ul><li>treat with weight loss, diet and exercise </li></ul></ul><ul><ul><li>oral medications improve insulin secretion or target cell sensitivity </li></ul></ul>
  39. 39. Pathology of Diabetes <ul><li>Acute pathology: cannot absorb glucose, breakdown fat and proteins (weight loss, weakness) </li></ul><ul><ul><li>fat catabolism  FFA’s in blood and ketone bodies </li></ul></ul><ul><ul><li>ketonuria  osmotic diuresis, loss of Na + and K + </li></ul></ul><ul><ul><li>ketoacidosis occurs as ketones  blood pH </li></ul></ul><ul><ul><ul><li>causes dyspnea and eventually diabetic coma </li></ul></ul></ul><ul><li>Chronic pathology </li></ul><ul><ul><li>chronic hyperglycemia leads to neuropathy and cardiovascular damage from atherosclerosis </li></ul></ul><ul><ul><ul><li>retina and kidneys (common in type I), atherosclerosis leads to heart failure (common in type II), and gangrene </li></ul></ul></ul>
  40. 40. Hyperinsulinism <ul><li>From excess insulin injection or pancreatic islet tumor </li></ul><ul><li>Causes hypoglycemia, weakness and hunger </li></ul><ul><ul><li>triggers secretion of epinephrine, GH and glucagon </li></ul></ul><ul><ul><ul><li>side effects: anxiety, sweating and  HR </li></ul></ul></ul><ul><li>Insulin shock </li></ul><ul><ul><li>uncorrected hyperinsulinism with disorientation, convulsions or unconsciousness </li></ul></ul>
  41. 41. Ovary <ul><li>Granulosa cells </li></ul><ul><ul><li>produces estradiol, first half of cycle </li></ul></ul><ul><li>Corpus luteum </li></ul><ul><ul><li>follicle after ovulation </li></ul></ul><ul><ul><li>produce estradiol and progesterone </li></ul></ul><ul><ul><ul><li>Functions of estradiol and progesterone </li></ul></ul></ul><ul><ul><ul><ul><li>development of female reproductive system and physique including bone growth </li></ul></ul></ul></ul><ul><ul><ul><ul><li>regulate menstrual cycle, sustain pregnancy </li></ul></ul></ul></ul><ul><ul><ul><ul><li>prepare mammary glands for lactation </li></ul></ul></ul></ul><ul><li>Both secrete inhibin: suppresses FSH secretion </li></ul>
  42. 42. Testes <ul><li>Interstitial cells (between seminiferous tubules) </li></ul><ul><ul><li>produce testosterone and estrogen </li></ul></ul><ul><li>Functions </li></ul><ul><ul><li>development of male reproductive system and physique </li></ul></ul><ul><ul><li>sustains sperm production and sex drive </li></ul></ul><ul><li>Sustentacular sertoli cells </li></ul><ul><ul><li>secrete inhibin which suppresses FSH & stabilizes sperm production rates </li></ul></ul>
  43. 43. Endocrine Functions of Other Organs <ul><li>Heart – </li></ul><ul><ul><li>atrial natriuretic peptide (ANP) released with an  in BP </li></ul></ul><ul><ul><li> blood volume and  BP by  Na + and H 2 O loss by kidneys </li></ul></ul><ul><li>Skin - helps produce vitamin D 3  calcitriol (  blood Ca) </li></ul><ul><li>Liver </li></ul><ul><ul><li>15% of erythropoietin (stimulates bone marrow) </li></ul></ul><ul><ul><li>angiotensinogen (a prohormone) </li></ul></ul><ul><ul><ul><li>precursor of angiotensin II   BP </li></ul></ul></ul><ul><ul><li>source of IGF-I (works with GH) </li></ul></ul><ul><ul><li>converts vitamin D3 to calcidiol </li></ul></ul><ul><ul><li>Hepcidin – promotes intestinal absorption of iron </li></ul></ul>
  44. 44. Endocrine Functions of Other Organs <ul><li>Kidneys </li></ul><ul><ul><li>erythropoietin – stimulates production of RBC’s </li></ul></ul><ul><ul><li>convert angiotensinogen to angiotensin I </li></ul></ul><ul><ul><li>converts calcidiol to calcitriol (active form of vitamin D) </li></ul></ul><ul><ul><ul><li> absorption by intestine and inhibits loss in the urine </li></ul></ul></ul><ul><ul><ul><li>more Ca 2+ available for bone deposition </li></ul></ul></ul><ul><li>Stomach and small intestines (10 enteric hormones) </li></ul><ul><ul><li>coordinate digestive motility and secretion </li></ul></ul><ul><li>Placenta </li></ul><ul><ul><li>secretes estrogen, progesterone and others </li></ul></ul><ul><ul><ul><li>regulate pregnancy, stimulate development of fetus and mammary glands </li></ul></ul></ul>
  45. 45. Hormone Chemistry <ul><li>Steroids </li></ul><ul><ul><li>derived from cholesterol </li></ul></ul><ul><ul><li>sex steroids, corticosteroids </li></ul></ul><ul><li>Peptides and glycoproteins </li></ul><ul><ul><li>OT, ADH; all releasing and inhibiting hormones of hypothalamus; most of anterior pituitary hormones </li></ul></ul><ul><li>Monoamines (biogenic amines) </li></ul><ul><ul><li>derived from amino acids </li></ul></ul><ul><ul><ul><li>catecholamines (norepinephrine, epinephrine, dopamine) and thyroid hormones </li></ul></ul></ul>
  46. 46. Hormone Synthesis: Steroid Hormones <ul><li>Synthesized from cholesterol – differs in functional groups attached to 4-ringed steroid backbone </li></ul>
  47. 47. Hormone Transport <ul><li>Monoamines and peptides are hydrophilic </li></ul><ul><ul><li>mix easily with blood plasma </li></ul></ul><ul><li>Steroids and thyroid hormone are hydrophobic </li></ul><ul><ul><li>must bind to transport proteins for transport </li></ul></ul><ul><ul><li>bound hormone - attached to transport protein, </li></ul></ul><ul><ul><ul><li>prolongs half-life to weeks </li></ul></ul></ul><ul><ul><ul><li>protects from enzymes and kidney filtration </li></ul></ul></ul><ul><ul><li>unbound hormone leaves capillary to reach target cell (half-life a few minutes) </li></ul></ul><ul><li>Transport proteins in blood plasma </li></ul><ul><ul><li>albumin, thyretin and TGB (thyroxine binding globulin) bind to thyroid hormone </li></ul></ul><ul><ul><li>steroid hormones bind to globulins (transcortin) </li></ul></ul><ul><ul><li>aldosterone - no transport protein, 20 min. half-life </li></ul></ul>
  48. 48. Hormone Receptors <ul><li>Located on plasma membrane, mitochondria, other organelles, or in nucleus </li></ul><ul><li>Usually thousands for given hormone </li></ul><ul><ul><li>hormone binding turns metabolic pathways on or off </li></ul></ul><ul><li>Exhibit specificity and saturation </li></ul>
  49. 49. Hormone Mode of Action <ul><li>Hydrophobic hormones </li></ul><ul><ul><li>penetrate plasma membrane – enter nucleus </li></ul></ul><ul><li>Hydrophilic hormones </li></ul><ul><ul><li>must bind to cell-surface receptors </li></ul></ul>
  50. 50. Hormone Clearance <ul><li>Hormone signals must be turned off </li></ul><ul><li>Take up and degraded by liver and kidney </li></ul><ul><li>Excreted in bile or urine </li></ul><ul><li>Metabolic clearance rate (MCR) </li></ul><ul><li>Half-life - time required to clear 50% of hormone </li></ul>
  51. 51. Hormone Interactions <ul><li>Most cells sensitive to more than one hormone and exhibit interactive effects </li></ul><ul><li>Synergistic effects </li></ul><ul><li>Permissive effects </li></ul><ul><ul><li>one hormone enhances response to a second hormone </li></ul></ul><ul><li>Antagonistic effects </li></ul>
  52. 52. Stress and Adaptation <ul><li>Stress </li></ul><ul><ul><li>upsets homeostasis and threatens well-being </li></ul></ul><ul><li>General adaptation syndrome </li></ul><ul><ul><li>way body reacts to stress </li></ul></ul><ul><ul><li>occurs in 3 stages </li></ul></ul><ul><ul><ul><li>alarm reaction </li></ul></ul></ul><ul><ul><ul><li>stage of resistance </li></ul></ul></ul><ul><ul><ul><li>stage of exhaustion </li></ul></ul></ul>
  53. 53. Alarm Reaction <ul><li>Initial response </li></ul><ul><li> epinephrine and norepinephrine levels </li></ul><ul><li> HR and  BP </li></ul><ul><li> blood glucose levels </li></ul><ul><li>Sodium and water retention (aldosterone) </li></ul>
  54. 54. Stage of Resistance <ul><li>After a few hours, glycogen reserves gone </li></ul><ul><li> ACTH and cortisol levels </li></ul><ul><li>Fat and protein breakdown </li></ul><ul><li>Gluconeogenesis </li></ul><ul><li>Depressed immune function </li></ul><ul><li>Susceptibility to infection and ulcers </li></ul>
  55. 55. Stage of Exhaustion <ul><li>Stress that continues until fat reserves are gone </li></ul><ul><li>Protein breakdown and muscle wasting </li></ul><ul><li>Loss of glucose homeostasis </li></ul><ul><li>Hypertension and electrolyte imbalances (loss of K + and H + ) </li></ul><ul><li>Hypokalemia and alkalosis leads to death </li></ul>
  56. 56. Paracrine Secretions <ul><li>Chemical messengers that diffuse short distances and stimulate nearby cells </li></ul><ul><ul><li>not produced in neurons or transported in blood </li></ul></ul><ul><li>Examples and their functions </li></ul><ul><ul><li>histamine </li></ul></ul><ul><ul><ul><li>from mast cells in connective tissue </li></ul></ul></ul><ul><ul><ul><li>causes relaxation of blood vessel smooth muscle </li></ul></ul></ul><ul><ul><li>nitric oxide </li></ul></ul><ul><ul><ul><li>from endothelium of blood vessels, causes vasodilation </li></ul></ul></ul><ul><ul><li>somatostatin </li></ul></ul><ul><ul><ul><li>inhibits secretion of islet alpha and beta cells </li></ul></ul></ul><ul><ul><li>catecholamines </li></ul></ul><ul><ul><ul><li>diffuse from adrenal medulla to cortex </li></ul></ul></ul>
  57. 57. Eicosanoids: a Paracrine Secretion <ul><li>Leukotrienes </li></ul><ul><ul><li>mediates allergic and inflammatory reactions </li></ul></ul><ul><li>Prostacyclin (by cyclooxygenase) </li></ul><ul><ul><li>inhibits blood clotting and vasoconstriction </li></ul></ul><ul><li>Thromboxanes (by cyclooxygenase) </li></ul><ul><ul><li>produced by blood platelets after injury; override prostacyclin, stimulates vasoconstriction and clotting </li></ul></ul><ul><li>Prostaglandins (by cyclooxygenase) : diverse; includes </li></ul><ul><ul><li>PGE: relaxes smooth muscle in bladder, intestines, bronchioles, uterus and stimulates contraction of blood vessels </li></ul></ul><ul><ul><li>PGF: opposite effects </li></ul></ul>
  58. 58. Review <ul><li>Thyroid </li></ul><ul><li>Pancreas </li></ul><ul><li>Pineal </li></ul><ul><li>Thymus </li></ul><ul><li>melatonin </li></ul><ul><li>thymopoietin </li></ul><ul><li>calcitonin </li></ul><ul><li>glucagon </li></ul>
  59. 59. <ul><li>FSH </li></ul><ul><li>GnRH </li></ul><ul><li>ADH </li></ul><ul><li>Estrogen </li></ul><ul><li>OT </li></ul><ul><li>LH </li></ul><ul><li>PTH </li></ul><ul><li>Parathyroid hormone </li></ul><ul><li>Antidiuretic hormone </li></ul><ul><li>Luteinizing hormone </li></ul><ul><li>Follicle stimulating hormone </li></ul><ul><li>Oxytoxin </li></ul><ul><li>Gonadotropin releasing hormone </li></ul><ul><li>Estrogen </li></ul>