Endocrine functions of the pancreas, pituitary and pineal glands 1/13

1. Endocrine functions of the pancreas, pituitary and pineal glands 1/13 • How do the three types of diabetes differ? • Why do hormonal responses change? • How does the hypothalmus regulate hormone release? • What two hormones are created by the neurohypophysis? • What six hormones are created by the adenohypophysis? • How are hormones synthesized? • What hormones are produced by the gonads? • How does the pineal gland determine wakefulness?

2. Practice Quiz for Monday and Wednesday’snotes • _______is a second messenger that increases intracellular calcium and is produced by the enzyme phospholipase-C. • IP3 b) cyclicAMP c) Diacylglycerol d) Sodium • Aldosterone is a steroid produced in what specific part of the adrenal gland? • Medulla b) Cortex c) Zona glomerulosa d) Kidney • Which receptor for epinephrine in causes fatty acids to be released from adipocytes as part of the Fight-or-Flight response? • Alpha-1 b) Alpha-2 c) Beta-1 d) Beta-2 e) Beta-3 • Cholesterol is not a precursor to what adrenal hormone? a) Cortisol b) Aldosterone c) DHEA d) Epinephrine e) Insulin

3. THE THREE TYPES OF DIABETES MELLITUS RESULT FROM EITHER AN INABILITY TO SECRETE INSULIN OR THE INABILITY OF SENSITIVE CELLS TO DETECT INSULIN. • Type I, IDDM: B-cells destroyed by autoimmune disease, reflux from bile duct, infection, or exocrine digestion • Sensitive cells like heart, liver, adipocytes, muscle need insulin and insulin receptors to let glucose enter the cytosol! • See tutorial: http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/pancreas/index.html • IDEA: save glucose for the brain during fasting: glucose dependent • COST: Without insulin, the glucose stays in bloodHyperglycemia • Why is Hyperglycemia a Problem? • Hemes and proteins glycosylated = loss of function! • Blindness, Oxidative stress and Vasoconstriction due to glycosylation! • Glucose is normally reabsorbed by the PCT of the nephron, if too much goes to the kidney it is not reabsorbed and it stays in the filtrate/urine • Diabetes Insipidus no ADH release from posterior pituitary! (no glucose in urine)

4. IDDM (type-I) is usually juvenile in onset, and requires insulin injections for life because beta cells can’t grow back! • Dependent Cells Can Starve without insulin!>>So they must metabolize fatty acids and ketones because these are less insulin dependent. • Non-sugar metabolites cause metabolic acidosis! • Fatty acid metabolism and excess blood glucose result in hepatic/heart/renal disease • These individuals often BECOME obese because their brain thinks they are starving, when they just cant use the food that’s there! • Hyperinsulinemia: overdose of replacement insulin causing hypoglycemia and neural tissue starvation. What would happen to your blood glucose if too much insulin was administered? Why do diabetics often “carry a candy bar”?

5. Type II or Non-insulin Dependent Diabetes Mellitus occurs when adipoctyes (mostly) stop responding to insulin, often as a result of energy excess. • Same Symptoms: polyuria, polydipsia, polyphagia. • +urine +thirst +eating • why? why? why? • Risk Factors: Age, Heredity(family/cultural), Obesity • Onset typically after age 40, now days it is often seen in obese college-age and younger persons. • Traditionally Adult onset, but not any more (how about insulin resistance in child with a BMI of 80?) • Adipocytes and other cells fail to respond to insulin and glucose influx after a meal becomes very slow, so glucose has nowhere to go….it accumulates in the blood causing hyperglycemia. • Treat with exercise and better diet. Gestational Diabetes is the “third” type- it occurs in transitory nature during pregnancy Test with an OGTT-oral glucose tolerance test

6. Cellular responses to hormones/drugs can change. WHY IS THIS IMPORTANT???? • Up Regulation: exposure improves future sensitivity! • Oxytocin and increasing numbers of receptors as birth approachesMore receptors More contractile force! • Down Regulation: exposure decreases future sensitivity • Insulin/Obesity: reduced receptors causes Type II diabetes • Fewer hormone receptors Less ability to remove glucose from blood! • How does receptor up/down regulation explain why a drug may work at first, but not later? • Hormone/Second Messenger Destruction: Cells can also learn to destroy hormones and 2nd messengers more rapidly. • Phosphodiesterase: stops cAMP activity • If a cell makes more PDE, you need to use more hormone to get effect!

7. Cellular responses to hormones/drugs can change. WHY IS THIS IMPORTANT???? • Dosage: Physiological vs. Pharmacological • How much is created and how much is required for what effects? • Why might low level or high level hormone releases give different effects? • Consider ADH effects with moderate or severe dehydration! • Do two hormones work together or against each other? • Synergistic (same) Effects: Oxytocin and Prostaglandins work together in uterus! • Antagonistic (against) Effects: Glucagon vs. Insulin work against each other in liver!

8. The pituitary gland is composed to two parts: 1) Neurohypophysis: connected to hypothalamus by axons.2) Adenohypophysis: a portal system of fenestrated capillaries supplies it with hypothalamic releasing hormones. Fenestration make these 1st capillaries very permeable to the releasing hormones!!! The neurohypophysis consists of a set of nerve endings that release their hormones directly into the blood. These hormones are synthesized in the hypothalamus and travel via axonal TX. Fenestrations also make this second set permeable too!

9. HOW DOES THE HYPOTHALMUS REGULATE PITUITARY FUNCTION? • Hypothalamus location: floor and walls of 3rd Ventricle • Hypophysis (pituitary) sits in the sella turica of the sphenoid below the hypothalamus. • Hypothalamus and Hypophysis are connected by the infundibulum or stalk. • Posterior Pituitary (Neurohypophysis): Direct release of hormones made in hypothalamus into fenestrated capillaries. • Anterior Pituitary (Adenohypophysis): Hypothalamic releasing/inhibiting hormones required to promote release a second hormone from Ant. Pit (REQ=> Portal Circulatory Structure!)

10. Posterior Pituitary: What pituitary hormones regulate child birth and water homeostasis/blood pressure? Two hypothalamic nuclei create two sets of hormones that are released into the blood stream at the neurophypophysis: • Paraventricular Nucleus: Oxytocin:child birth/milk • Saladin claims importance questionable: Be Careful! • Days before birth OT receptors in uterus increase! • Increased receptorsstronger SMC contractionsDelivery! • OT>PL>>IP3>>Ca++>>Contraction and Prostaglandins • Supraventricular Nucleus: Anti-Diuretic Hormone (ADH or Vasopressin) Maintains blood pressure! • +Water Reabsorption in kidney+Blood Volume+Blood Pressure • Constrictor effect only at very high levels +Blood Pressure. • Adjusts plasma volume and osmolarity. • Diabetes Insipidus often occurs when lesions form in tracts • Note: no glucose in the urine!

11. THE HYPOTHALMUS CONTROLS ANTERIOR PITUITARY FUNCTION WITH RELEASING/INHIBITING HORMONES THAT ONLY WORK IF THE PORTAL SYSTEM IS INTACT! • Releasing/Inhibiting hormones released to blood/capillaries in hypothalamus (portal system #1) and pulled out at second capillary bed in anterior pituitary. • 6 Ant. Pit. Hormones: FSH,LH,TSH,ACTH,PRL,GH Respective Hypothalamic Hormones Control Release: • 1) Thyrotropin Releasing Hormone (TRH)+TSH and PRL • 2) Prolactin Releasing Factor (PRF)+PRL • 3) Prolactin Inhibitory Factor (PIF)-PRL • 4) Corticotropin Releasing Factor(CRH)++ACTH • 5) Growth Hormone Releasing Hormone (GnRH)+GH • 6) Gonadotropin Releasing Hormone+FSH/LH • 6) Somatostatin (GNIH)  -GH AND -TSH

12. FOUR TROPHIC HORMONES ARE RELEASED FROM THE ANTERIOR PITUITARY: ACTH, PRL,TSH AND GH • Adrenocorticotrophic hormone (ACTH)-Stimulates adrenal cortex and glucocorticoid secretion for stress management. • Prolactin (PRL)-Stimulates milk synthesis following birth. • Thyroid stimulating Hormone (TSH)-Stimulates thyroid gland to release T3/T4 and create a calorigenic state in body>>>HEAT or growth dung infancy • Growth Hormone (GH)-Stimulates cell division, protein synthesis and bone growth Promotes FA metabolism: saves glucose for glycogen synthesis and storage. Related to Gigantism, Acromegally and Dwarfism • Pituitary tumors can occur in a pituitary cell line for anyone of these hormones, this type of cancer is very tough to treat with radiation of surgery! WHY???

13. How does Prolactin play a role in making the cows come home?

14. THE TWO ANTERIOR PITUITARY GONADOTROPHIC HORMONES PROMOTE SEX STEROID SYNTHESIS. LH is Luteinizing Hormone: LH (not FSH) Stimulates testosterone production by Leydig cells in testes Stimulates initial estrogen secretion from follicle and corpus luteum FSH is Follicle Stimulating Hormone: FSH (not LH) Stimulates sperm maturation at testes -Stimulates egg maturation/ovulation Classic Feedback Loop in Women leading to Ovulation: • GnRH FSH and LH + follicle/estradiol+GnRH LH Surge OvulationCorpusluteum makes progesterone and some estradiol to maintain endometrium

15. GONADS RESPOND TO FSH/LH AND SECRETE MANY SEX STEROIDS WITH TWO IMPORTANT ONES BEING: ESTRADIOL AND TESTOSTERONE. • Males: produce testosterone in response to LH Promotes Protein Synthesis, Stops growth plate DHEA (dehydroxyepandiosterone) is a precursor for testosterone synthesis • FSH release is inhibited because high levels of testosterone inhibit GnRH release from hypothalamus • Females: produce estrogen in response to FSH Estradiol causes follicular maturation/release Newly formed corpus luteum makes progestrone in addition to continued estrogen • Menopause occurs later in life when even extremely high levels of FSH are unable to increase estradiol secretion and follicular maturation.

16. Sex Steroid Synthesis in gonads of males and females is very similar, difference is that in females testosterone is further metabolized to make estradiol. Smaller amounts of synthesis also occurs in the zona reticularis of the adrenal cortex.

17. THE PINEAL GLAND IS OUR BIOLOGICAL CLOCK: IT CONTROLS CIRCADIAN AND SEASONAL RHYTHMS. • Located in back/bottom area of brain of “mammals” on roof of third ventricle. • “Circadian Rhythms” are daily cycles of hormone production. • Rhythms can also occur on a monthly and yearly cycle. • During the day a modified amino acid called serotonin is released (wakefulness). • “Wakefulness” is the opposite of “depression” • Many antidepressant drugs work by reducing serotonin destruction/removal improve “mood” and • At night serotonin is converted into melatonin which is a hormone that causes drowsiness and sleep. • Why does honey on toast help you wake up or dream? • This is source of “jet-lag” symptoms!

18. CIRCADIAN RHYTHMS OF HORMONE PRODUCTION CAN BE VERY IMPORTANT IN EXPLAINING WHY ASTHMA OR HEART ATTACKS ARE MORE COMMON AT CERTAIN TIMES OF THE DAY. • 1) Remember that EPI and NE help dilate cardiac blood vessels and airways *How does this help during exercise? • 3) Remember that cortisol helps constrict airways! • How does this help clean air when you sleep? • 4) When are asthma/heart attacks more common? • When is cortisol or EPI/NE more prominent? • Many anti-depressive drugs mimic serotonin/melatonin • Many anti-depressive drugs prevent the destruction or removal of serotonin (PROZAC blocks pumps). • Seasonal Affective Disorder and PreMenstrual Syndrome are two classic examples of disorders that may respond to modified serotonin release, uptake or destruction.