Diabetes mellitusPineal GlandThymus GlandGonadsOvariesTestesDiseases associated with the Thyroid GlandAddison’s DiseaseHormone ChemistryHormone Synthesis -SteroidsHormone Synthesis - PeptidesHormone Synthesis - MonoaminesSynthesis of THHormone TransportMode of ActionThyroid Hormone SpecificallyPeptides and CatecholaminesEnzyme AmplificationHormone ClearanceModulation of Cell SensitivityHormone interactionsDiabetes mellitusNormal blood glucose levels = 80 to 120 mg/100 ml of bloodWhen not absorbed to rises, spills into urineGlucose is expelled, water follows leading to dehydrationNot using glucose, fats and proteins usedLoss of weight and issue with infectionsBlood becomes acidic (acidosis) due to ketones in blood (ketosis)Two typesType II – adult onset, Insulin resistant, insulin produce, cells don’t recognize. Treated with diet and drugs to help with insulin sensitivityType I – juvenile, no insulin made. Treated with pump or injectionsPineal GlandIn brain, function not completely understoodMelatonin – sleep triggerPeak levels at night, make sleepyLowest levels at noonSecretion highest age 1-5, 75% smaller in adolescenceHelps regulate mating behaviors in animalsHumans coordinates hormones of fertility○Inhibits reproductive system – inhibits gonadotropinsThymus GlandUpper thorax, posterior to sternumThymosin and thymopoietinNormal development of T cells, lymphocytesDecreases in size throughout life, mostly fibrous connective and fat by old age.What effect on immune system?GonadsSex hormones same as adrenal cortexOvaries – Ova (exocrine)Estrogen – sex characteristics of womenProgesterone and estrogen – breast development and menstrual cycleTestes – Sperm (exocrine)Testosterone – sex characteristic of men, voice, muscle, sex drive, continuing sperm productionOvariesEach follicle contains egg with Granulosa cellsGranulosa cells secrete estrogen called estradiol ½ of menstrual cycle, copus lutem secretes estradiol and progesterone after ovulation and 8-12wks of pregnancyReproductive system developmentFeminine physique,Bone growthRegulate menstrual cycleSustain pregnancyFollicle and corpus luteum secrete inhibin suppresses FSH via neg feedbackTestesInterstitial cells secrete testosterone and other androgensMale reproductive systemMale physiqueSex driveSperm production and sexual instinct all lifeSustentacular cells secrete inhibinInhibits FSH, regulates sperm productionDiseases associated with the Thyroid GlandFigure 9.8GoiterFigure 9.9Grave’s DiseaseexophthalmosHyperthyroidism – rapid heartbeat, high metabolism, agitated, hard to relax, thyroid gland enlarges, eyes bulge. Treated with surgery, or drugs.Hypothyroidism – results in myxedema, physically and metally sluggish, puffy, dry skin, obese, low temp. Treated with ThyroxineAddison’s DiseaseHyperpigmentationBronze coloring of skinAldosterone is low, water and Na lost, electrolyte problemsMuscle weaknessHormone ChemistryMost are eitherSteroid hormone – derived from cholesterol○Sex steroids, corticosteroids, Calcitriol (not steroid but derived from one)Peptide hormones – chains of 3-200+ aa○Hormones from Post Pit, most releasing and stimulating hormones from Hypothalamus, most hormones from Ant PitMonoamines – chain of aa and amino group○epinephrine, NE, dopamine, melatonin, and THHormone Synthesis -SteroidsAll made from either cholesterol or AASteroidsSynthesized from cholesterol, functional group attached to 4 ring structure differsHormone Synthesis - PeptidesGene transcribed to mRNA, mRNA translated into preprohormonesSmall chain of AA direct preprohormone to ER, snipped off = prohormone, inactiveOff to the Golgi for modification and packagingHormone Synthesis - MonoaminesFrom AA that retain amino groupMelatonin from Tryptophan, others from TyrosineTH unique- TH comes from a larger protein called Thyroglobulin, not part of finished TH○TH two tyrosine linked together○TH requires IodineSynthesis of TH1) ______ cells secrete thyroglobulin into lumen of follicle = colloid2) I absorbed by follicular cells from blood, transported into lumen3) I added to tyrosine of thyroglobulin = monoiodotyrosine (MIT)4) Another I added, diiodotyrosine (DIT)5) DIT + either MIT or DIT6) DIT + MIT = T3, DIT + DIT = T4 but both still connected to Thyroglobulin7) TSH stimulated follicular cells to take up colloid by pinocytosis, lysosome fuses, cleaves off thyroglobulinGet 10%T3 and 90%T4Hormone TransportTransport via blood, hydrophilicPeptides and monoamines are good, hydrophilic as wellWhat about Steroids?○Need transport proteins – albumins and globulins from liverBound vs. Unbound○Transport ○Prolongs ½ lifeTH over 99% bound, removal of Thyroid, TH up to 2 weeksAldosterone - ½ life twenty minutesFigure 9.1Mode of ActionDirect Gene Activation – lipid soluble, steroids and thyroid hormoneSecond-Messenger System – water soluble, nonsteroidalDifferent cellular responses to same hormoneThyroid Hormone SpecificallyCarried by transport TBG, dissociates in bloodT3 and T4 enter cytoplasmT4 – I cleaved ->T3Mitochondria – stimulate aerobic respirationRibosomes – incr. mRNA translationReceptors on chromatin, incr. gene transcription○Sodium potassium pumpPeptides and CatecholaminesHydrophilicTwo second messenger systemscAMP and Diacylglycerol and Inositol Triphosphate (IP3)Enzyme AmplificationHormones only needed in small amounts to get effect in cell needed due to cascade1 glucagon molecule trigger production of 1000 cAMP1 cAMP makes 1 kinase1 kinase activates 1000 enzyme moleculesEach enzyme activates 1000 end product1 glucagon produced 1 billion end moleculesHormone ClearanceMost cleared by liver and kidneys, excreted in bile or urineSome degraded by target cellsBound take longer to clear than unboundMetabolic clearance rate (MCR) = rate hormone clearedHigher MCR shorter ½ lifeModulation of Cell SensitivityUp-regulation – target cell increases receptors for hormone to make itself more sensitiveUterus and OT for laborDown-regulation – reduction in receptors so target less sensitive to hormones,Happens when long exposure to high hormone levels○Cells of testis down regulate in response to high