Post on 02-Jan-2016
Embed Size (px)
DESCRIPTIONOptic chasm. infudibulum. Median eminence. Arterial blood supply. Posterior pituitary. Hypothalamo-pituitary portal vessels. Anterior pituitary. Endocrine cells. To venous circulation. To venous circulation. Short portal vessels. Arterial blood supply. Axon to primary - PowerPoint PPT Presentation
OpticchasminfudibulumArterial bloodsupplyHypothalamo-pituitaryportal vesselsAnteriorpituitaryEndocrinecellsTo venouscirculationShort portalvesselsArterial bloodsupplyTo venouscirculationPosteriorpituitaryMedianeminence
Transduction Pathways of Releasing HormonesHormonePathwayLocation of actionPKAaPIbCRHTRHGnRHAVPCorticotrope of anteriorpituitary (ACTH)Thyrotrope of anteriorpituitary (TSH)Gonadotrope of anteriorpituitary (LH & FSH)Corticotrope of anteriorpituitary; assists CRH inreleasing ACTH+++c
Transduction Pathways of Releasing Hormones (cont.)GHRHSomatostatinPRLHormonePathwayLocation of actionPKAaPIbSomatomammotropeof anterior pituitary (GH)+(?)Release inhibitorSomatomammotropeof anterior pituitary(inhibits GH release)+daPKA, protein kinase AbPI, phosphatidylinositol pathwaycThe increase of cytoplasmic calcium concentrationmay be important in the actions of PI stimulationdInhibitory pathway of PKA
Effects of hypophysectomy1. Cessation of growth & the retention of juvenile features.2. Atrophy of adrenal cortes (zona fasciculata).3. Atrophy of thyroid.4. Decreased gonadal function in the adult.5. Alterations in the metabolism of lipids, proteins, and carbohydrates.6. Blanching of pigment cells in the skin of the lower vertebrates (fishes, amphibians, & reptiles
Growth Hormone (GH)SomatotropinI. ChemistryStraight chain polypeptide of 191 AA (Two S-S bonds)Mole Weight: 22,000 deltonsProduced by somatotroph (acidophil) cellsPlasma Concentration 3-10 ng/mlCirculating half-life: 20-30 minutesBroken down by the liver
II. Biologic ActionsA. Supports Osteogenesis(Epiphyseal-diaphyseal plate)Stimulates release of peptide somatomedin from the liver1. Oversecretion (acidophilic adenoma)(a) Giantism(b) Acromegaly2. Undersecretion(a) Pituitary dwarf(b) Simmonds disease (hypophyseal cachexia)
Amino Acid Sequence of HGH
Facial changes in a patient with acromegaly.Panel at left shows appearance of normal youngwoman. Middle & right show effects of acromegalywith coarsening of facial features.
Hand of someone with acromegaly (left)placed next to normal hand (right).
Somatotropin (cont.)B. Promotes protein synthesis (anabolic effect)Retards AA catabolism: transport into cell.AA retention causes positive nitrogen - phosphate balance. Na+ + K+ excretion
C. Diabetogenic effect (Houssay animal)Blocks hexokinase
Somatotropin (cont.)Affects carbohydrate metabolism by:1. hyperglycemia2. Inhibiting insulin action3. muscle glycogen4. Production of permanent diabetes mellitus (destroys B cells)
Somatotropin (cont.)D. Peripheral mobilization of fats(Pharmacologic doses)[serum fatty acids]
E. Increase intestinal absorption of calciumF. Increase renal tubular reabsorption of phosphorus
Somatotropin (cont.)III. Regulation of releaseA. Stimulation (via Somatotropin Releasing Hormone) SRHDeficiency of energy substrate:1. Hypoglycemia2. Exercise3. Fasting4. Plasma protein5. Sleep
Somatotropin (cont.)B. Inhibition (via somatostatin) IH1. Serum glucose2. Cortisol3. REM sleep
Somatotropin (cont.)IV. Potential Clinical Use for Hypothalmic HormonesA. Somatotropin Releasing HormoneTreats GH deficiency effects-short statureB. Somatostatin (14 AA peptide)Treatment of acromegaly
Growth Curve% of totalgrowthAge (years)04812162020406080100
Age (years)04812261014Adult0.40.50.60.70.80.91.01.11.2Somatomedin Level (U/mL)(8)(6)(6)(4)(5)(5)(2)
AgeWt.Growth H. + thyroxineGrowth H.throxinecontrol
ProlactinChemistryUnbranched polypeptide of 198 AA (human). It has 3disulfide bridges and a mole wt. of ~ 25,000. Secreted byacidphil cells (lactotrophs) of the adenohypophysis. Theprolactins have a myriad of effects among vertebratesand hence a myriad of different names (lactogenic hormone;mammotrophin; galactin; luteotrophin; etc.) The N&Cterminals are similar to those in growth hormone.Half-life of 15-25 minutesSerum level 8 ng/mL female : 5 ng/mL male
Prolactin (cont.)Biologic ActionsA. Non-Humans1. Luteotropic effect (rats)- maintenance of the functional activity of the corpus luteum & release of progesterone (controlled by LH in humans.)2.Maternal behavior (rabbits)- injections of prolactin into non-pregnant rabbits results in nest building.
Ovine (sheep) prolactin. The black bars indicate disulfide bridges.
Prolactin (cont.)B. Human Functions1. Mammotrophic effect- stimulates the mammary epithelium to secrete milk (i.e. produce milk.)2. Affects function of adrenals, gonads, steroid synthesis, and lipolysis.
Prolactin (cont.)Regulation of ReleaseA. Secretion (PRH- Prolactin Releasing Hormone)1. Pregnancy- reaches peak during parturition2. Stimulation of nipples (nursing baby)3. Surgical or psychologic stress4. Coitus
Prolactin (cont.)B. Inhibition (PIH- Dopamine)1. Dopmine is a product of L-Dopa (used to treat Parkinsons disease- neurological disorder- tremors)2. Estrogen & progesterone- high levels during pregnancy inhibit action of prolactin. After birth, milk production increases.
PhysiologicalPathologicalPharmacologicalCauses of Increased Concentrationof Production in SerumSleepSuckingExerciseHypothalmic disorders,Chiari-Frommel syndromeRenal failureSexual intercourseEstrogensThyrotropin-releasing hormoneInsulin-induced hypoglycemiaHypothyroidismArginineParathormoneNelsons syndromeAdrenal insufficiencyEctopic production by tumorsStress (e.g., surgery)Pituitary stalk sectionsOral contraceptives e.g., sarcoid infiltration
CorticotropinAdrenocorticotrophic Hormone (ACTH)ChemistryStraight chain polypeptide of 39 AA & a mole weight of 4,500.It is secreted by corticotroph cells (basophil). ACTH has a 13AA sequence from its N-terminal which is identical with MSH.It therefore has a natural tendency to melanosize cells likeB-lipotrophin (AA 41-58)Biologic Actions1. ACTH controls the release of glucocorticoids (cortisol and corticosterone) from the zona fasciculata of the adrenal cortex.2. Release of adrenal androgens
Zona GlomerulosaZonaFasciculataMedullaZona Reticularis
Regulation of Release Almost any type of physical or mental stresscauses the release of CRH from the hypoth-alamus. This causes the release of ACTHwhich glucocorticods.
Regulation of Release (cont.)BIOASSAYS1. Depletion of ascorbic acid (vitamin C).a) formation of collagenb) [iron] in body fluidsc) Scurvy (20-30 week deficiency) Failure of wounds to heal ( collagen) Cessation of bone growth Fragile walls of blood vessels
(cont.)2. Depletion of cholesterol.3. Incubation methods: Incubate adrenal slices with ACTH. Measure cortisones produced. 4. Maintenance of adrenal weight in animals.
ThyrotropinI. CHEMISTRY:TSH, FSH, & LH are glycoproteins produced by basophil cells and having chemically dissimilar subunits non-covalently linked together.
Thyrotropin (cont.)Subunits:a) Alpha - this subunit is identical in the identical in the three hormones. b) Beta - provides hormonal specificity. Produced by thyrotroph (basophil) cells Mole wt. 26,000 Circulating half-life is 60 minutes Broken down by kidney
Thyrotropin (cont.)II. BIOLOGIC ACTIONS1. Maintenance of the structural and functional integreties of the thyroid gland. 2. Controls iodine uptake (iodide pump)3. Maintains normal secretory epithelium- low columnar.
Thyrotropin (cont.)4. Causes production and release of thyroxine.
Thyrotropin (cont.)III. Regulation of releaseA. Stimulation (via thyrotropin releasing hormone)Negative feedback1) thyroxine2) body temperatureB. Inhibition1) serum thyroxine2) body temperature
Thyrotropin (cont.)IV. Assay MethodsA. Bioassay1) height of secretory epithelium2) Number of colloid droplets in cells3) Iodine depletion in 1-day old chicks4) Uptake of radioactive iodineB. Radioimmunoassay
FolliculotropinFollicle Stimulating Hormone (FSH)ChemistrySame as Thyrotropin (produced by gonadotroph cells)Alpha= 92 AABeta= 118 AABiologic ActionA. Female1. Stimulates young ovarian follicles to develop multiple layers of granulosa cells & form antra.
Folliculotropin (cont.)2. Stimulate production of estrogen by developing follicleB. MaleStimulates the seminiferous tubules- spermatogenesisRegulation of releaseConcentration of circulating estrogens- negative feedback.Note: Both estrogen production & completed spermatogenesis require LH.
OOGONIA NUMBERS(Text P. 630)5 months of gestation = 7 million Birth = 2 million Puberty = 300,000 to 400,000Released during sexual maturity (40 years) = 480
Corpus albicansGerminal epitheliumCorpus luteumOvulationCorona radiataSecondary oocyteZona pellucida
Cumulus oophorousTimeTimeGraafian follicleAntrumPrimary follicle
Growing primary follicle
ESTROGENS (17 BETA ESTRADIOL)Biologic Actions 1. Act as growth hormones stimulating mitosis in the mammary glands and the female reproductive system (uterus and vagina).
ESTROGENS (cont.)2. Promote the deposition of fat in the breast, thighs and buttocks, thereby decreasing the specific gravity in females.
3. Promote the early closing of the growth plates.
epididymisEfferent ductulesSpermatic cordtestisSeminiferous tubulesRete testis withinmediastinum testis
InterstitialcellsGerminalepithelial cellsLumen of seminiferous tubuleBasementmembraneSpermatazoa
LutotropinInterstitial Cell StimulatingHormone (ICSH)ChemistrySame as ThyrotropinHalf-life of one hour
Alpha=96 AABeta=120 AA
Lutotropin (cont.)Biologic ActionA. Female1. Release of estrogen from developing follicle.2. Promotes ovulation. Ovulatory surge in concentration just before ovulation.3. Affects luteinization of ruptured follicle.4. Causes release of progesterone from corpus luteum
Lutotropin (cont.)Biologic ActionB. Male1. Affects spermatogenesis- completes process.2. Stimulates Leydig cells to produce testosterone.
Regulation of ReleaseNegative feedback with progesteroneNote: This is why HCG is needed during pregnancy