Y khoa, y dược - The endocrine system: Part B

16The Endocrine System: Part BThe Posterior Pituitary Contains axons of hypothalamic neuronsStores antidiuretic hormone (ADH) and oxytocinADH and oxytocin are released in response to nerve impulses OxytocinStimulates uterine contractions during childbirth by mobilizing Ca2+ through a PIP2-Ca2+ second-messenger systemAlso triggers milk ejection (“letdown” reflex) in women producing milkPlays a role in sexual arousal and orgasm in males and femalesAntidiuretic Hormone (ADH)Hypothalamic osmoreceptors respond to changes in the solute concentration of the bloodIf solute concentration is highOsmoreceptors depolarize and transmit impulses to hypothalamic neuronsADH is synthesized and released, inhibiting urine formationAntidiuretic Hormone (ADH)If solute concentration is lowADH is not released, allowing water loss Alcohol inhibits ADH release and causes copious urine outputHomeostatic Imbalances of ADH ADH deficiency—diabetes insipidus; huge output of urine and intense thirst ADH hypersecretion (after neurosurgery, trauma, or secreted by cancer cells)—syndrome of inappropriate ADH secretion (SIADH)Thyroid GlandConsists of two lateral lobes connected by a median mass called the isthmusComposed of follicles that produce the glycoprotein thyroglobulinColloid (thyroglobulin + iodine) fills the lumen of the follicles and is the precursor of thyroid hormoneParafollicular cells produce the hormone calcitoninFigure 16.8Thyroid Hormone (TH)Actually two related compoundsT4 (thyroxine); has 2 tyrosine molecules + 4 bound iodine atomsT3 (triiodothyronine); has 2 tyrosines + 3 bound iodine atomsThyroid HormoneMajor metabolic hormoneIncreases metabolic rate and heat production (calorigenic effect)Plays a role inMaintenance of blood pressureRegulation of tissue growthDevelopment of skeletal and nervous systemsReproductive capabilitiesSynthesis of Thyroid HormoneThyroglobulin is synthesized and discharged into the follicle lumenIodides (I–) are actively taken into the cell, oxidized to iodine (I2), and released into the lumenIodine attaches to tyrosine, mediated by peroxidase enzymesSynthesis of Thyroid HormoneIodinated tyrosines link together to form T3 and T4Colloid is endocytosed and combined with a lysosomeT3 and T4 are cleaved and diffuse into the bloodstreamFigure 16.9To peripheral tissuesT3T3T3T4T4LysosomeTyrosines (part of thyroglobulinmolecule)T4DIT (T2)IodineMIT (T1)Thyro-globulincolloidIodide (I–)RoughERCapillaryColloidColloid inlumen offollicleThyroid follicle cells Iodinated tyrosines arelinked together to form T3and T4. Iodideis oxidizedto iodine. Thyroglobulin colloid isendocytosed and combinedwith a lysosome. Lysosomal enzymes cleaveT4 and T3 from thyroglobulincolloid and hormones diffuseinto bloodstream. Iodide (I–) is trapped(actively transported in). Thyroglobulin is synthesized anddischarged into the follicle lumen. Iodine is attached to tyrosinein colloid, forming DIT and MIT.Golgiapparatus1234567Figure 16.9, step 1Tyrosines (part of thyroglobulinmolecule)RoughERCapillaryColloidColloid inlumen offollicleThyroid follicle cells Thyroglobulin is synthesized anddischarged into the follicle lumen.Golgiapparatus1Figure 16.9, step 2Tyrosines (part of thyroglobulinmolecule)Iodide (I–)RoughERCapillaryColloidColloid inlumen offollicleThyroid follicle cells Iodide (I–) is trapped(actively transported in). Thyroglobulin is synthesized anddischarged into the follicle lumen.Golgiapparatus12Figure 16.9, step 3Tyrosines (part of thyroglobulinmolecule)IodineIodide (I–)RoughERCapillaryColloidColloid inlumen offollicleThyroid follicle cells Iodideis oxidizedto iodine. Iodide (I–) is trapped(actively transported in). Thyroglobulin is synthesized anddischarged into the follicle lumen.Golgiapparatus123Figure 16.9, step 4Tyrosines (part of thyroglobulinmolecule)DIT (T2)IodineMIT (T1)Thyro-globulincolloidIodide (I–)RoughERCapillaryColloidColloid inlumen offollicleThyroid follicle cells Iodideis oxidizedto iodine. Iodide (I–) is trapped(actively transported in). Thyroglobulin is synthesized anddischarged into the follicle lumen. Iodine is attached to tyrosinein colloid, forming DIT and MIT.Golgiapparatus1234Figure 16.9, step 5T3Tyrosines (part of thyroglobulinmolecule)T4DIT (T2)IodineMIT (T1)Thyro-globulincolloidIodide (I–)RoughERCapillaryColloidColloid inlumen offollicleThyroid follicle cells Iodinated tyrosines arelinked together to form T3and T4. Iodideis oxidizedto iodine. Iodide (I–) is trapped(actively transported in). Thyroglobulin is synthesized anddischarged into the follicle lumen. Iodine is attached to tyrosinein colloid, forming DIT and MIT.Golgiapparatus12345Figure 16.9, step 6T3LysosomeTyrosines (part of thyroglobulinmolecule)T4DIT (T2)IodineMIT (T1)Thyro-globulincolloidIodide (I–)RoughERCapillaryColloidColloid inlumen offollicleThyroid follicle cells Iodinated tyrosines arelinked together to form T3and T4. Iodideis oxidizedto iodine. Thyroglobulin colloid isendocytosed and combinedwith a lysosome. Iodide (I–) is trapped(actively transported in). Thyroglobulin is synthesized anddischarged into the follicle lumen. Iodine is attached to tyrosinein colloid, forming DIT and MIT.Golgiapparatus123456Figure 16.9, step 7To peripheral tissuesT3T3T3T4T4LysosomeTyrosines (part of thyroglobulinmolecule)T4DIT (T2)IodineMIT (T1)Thyro-globulincolloidIodide (I–)RoughERCapillaryColloidColloid inlumen offollicleThyroid follicle cells Iodinated tyrosines arelinked together to form T3and T4. Iodideis oxidizedto iodine. Thyroglobulin colloid isendocytosed and combinedwith a lysosome. Lysosomal enzymes cleaveT4 and T3 from thyroglobulincolloid and hormones diffuseinto bloodstream. Iodide (I–) is trapped(actively transported in). Thyroglobulin is synthesized anddischarged into the follicle lumen. Iodine is attached to tyrosinein colloid, forming DIT and MIT.Golgiapparatus1234567Transport and Regulation of THT4 and T3 are transported by thyroxine-binding globulins (TBGs) Both bind to target receptors, but T3 is ten times more active than T4Peripheral tissues convert T4 to T3Transport and Regulation of THNegative feedback regulation of TH release Rising TH levels provide negative feedback inhibition on release of TSHHypothalamic thyrotropin-releasing hormone (TRH) can overcome the negative feedback during pregnancy or exposure to coldFigure 16.7HypothalamusAnterior pituitaryThyroid glandThyroidhormonesTSHTRHTarget cellsStimulatesInhibitsHomeostatic Imbalances of THHyposecretion in adults—myxedema; endemic goiter if due to lack of iodineHyposecretion in infants—cretinismHypersecretion—Graves’ diseaseFigure 16.10CalcitoninProduced by parafollicular (C) cellsAntagonist to parathyroid hormone (PTH)Inhibits osteoclast activity and release of Ca2+ from bone matrixCalcitoninStimulates Ca2+ uptake and incorporation into bone matrixRegulated by a humoral (Ca2+ concentration in the blood) negative feedback mechanismNo important role in humans; removal of thyroid (and its C cells) does not affect Ca2+ homeostasisParathyroid GlandsFour to eight tiny glands embedded in the posterior aspect of the thyroidContain oxyphil cells (function unknown) and chief cells that secrete parathyroid hormone (PTH) or parathormonePTH—most important hormone in Ca2+ homeostasisFigure 16.11(b)CapillaryChiefcells(secreteparathyroidhormone)OxyphilcellsPharynx(posterioraspect)ThyroidglandParathyroidglandsTracheaEsophagus(a)Parathyroid HormoneFunctionsStimulates osteoclasts to digest bone matrix Enhances reabsorption of Ca2+ and secretion of phosphate by the kidneysPromotes activation of vitamin D (by the kidneys); increases absorption of Ca2+ by intestinal mucosaNegative feedback control: rising Ca2+ in the blood inhibits PTH release Figure 16.12IntestineKidneyBloodstreamHypocalcemia (low blood Ca2+) stimulatesparathyroid glands to release PTH.Rising Ca2+ inblood inhibitsPTH release.1 PTH activatesosteoclasts: Ca2+and PO43S releasedinto blood. 2 PTH increasesCa2+ reabsorptionin kidneytubules.3 PTH promoteskidney’s activation of vitamin D,which increases Ca2+ absorptionfrom food.BoneCa2+ ionsPTH MoleculesHomeostatic Imbalances of PTHHyperparathyroidism due to tumorBones soften and deformElevated Ca2+ depresses the nervous system and contributes to formation of kidney stonesHypoparathyroidism following gland trauma or removalResults in tetany, respiratory paralysis, and deathAdrenal (Suprarenal) GlandsPaired, pyramid-shaped organs atop the kidneysStructurally and functionally, they are two glands in oneAdrenal medulla—nervous tissue; part of the sympathetic nervous systemAdrenal cortex—three layers of glandular tissue that synthesize and secrete corticosteroidsAdrenal CortexThree layers and the corticosteroids producedZona glomerulosa—mineralocorticoidsZona fasciculata—glucocorticoidsZona reticularis—sex hormones, or gonadocorticoidsFigure 16.13a• CortexKidney• MedullaAdrenal glandCapsuleZonaglomerulosaZonafasciculataZonareticularisAdrenalmedulla(a) Drawing of the histology of the adrenal cortex and a portion of the adrenal medullaMedullaCortexMineralocorticoidsRegulate electrolytes (primarily Na+ and K+) in ECFImportance of Na+: affects ECF volume, blood volume, blood pressure, levels of other ionsImportance of K+: sets RMP of cellsAldosterone is the most potent mineralocorticoid Stimulates Na+ reabsorption and water retention by the kidneysMechanisms of Aldosterone SecretionRenin-angiotensin mechanism: decreased blood pressure stimulates kidneys to release renin, triggers formation of angiotensin II, a potent stimulator of aldosterone release Plasma concentration of K+: Increased K+ directly influences the zona glomerulosa cells to release aldosteroneACTH: causes small increases of aldosterone during stressAtrial natriuretic peptide (ANP): blocks renin and aldosterone secretion, to decrease blood pressureFigure 16.14Primary regulatorsOther factorsBlood volumeand/or bloodpressureAngiotensin IIBlood pressureand/or bloodvolumeK+ in bloodDirectstimulatingeffectReninInitiatescascadethatproducesKidneyHypo-thalamusHeartCRHAnteriorpituitaryZona glomerulosaof adrenal cortexEnhancedsecretionof aldosteroneTargetskidney tubulesAbsorption of Na+ andwater; increased K+ excretionBlood volumeand/or blood pressureInhibitoryeffectStressACTHAtrial natriureticpeptide (ANP)Homeostatic Imbalances of Aldosterone Aldosteronism—hypersecretion due to adrenal tumorsHypertension and edema due to excessive Na+Excretion of K+ leading to abnormal function of neurons and muscle Glucocorticoids (Cortisol)Keep blood sugar levels relatively constantMaintain blood pressure by increasing the action of vasoconstrictorsGlucocorticoids (Cortisol)Cortisol is the most significant glucocorticoidReleased in response to ACTH, patterns of eating and activity, and stressPrime metabolic effect is gluconeogenesis—formation of glucose from fats and proteinsPromotes rises in blood glucose, fatty acids, and amino acidsHomeostatic Imbalances of GlucocorticoidsHypersecretion—Cushing’s syndromeDepresses cartilage and bone formationInhibits inflammationDepresses the immune systemPromotes changes in cardiovascular, neural, and gastrointestinal functionHyposecretion—Addison’s diseaseAlso involves deficits in mineralocorticoidsDecrease in glucose and Na+ levelsWeight loss, severe dehydration, and hypotensionFigure 16.15Gonadocorticoids (Sex Hormones)Most are androgens (male sex hormones) that are converted to testosterone in tissue cells or estrogens in femalesMay contribute toThe onset of pubertyThe appearance of secondary sex characteristicsSex drive Adrenal MedullaChromaffin cells secrete epinephrine (80%) and norepinephrine (20%)These hormones causeBlood glucose levels to riseBlood vessels to constrictThe heart to beat fasterBlood to be diverted to the brain, heart, and skeletal muscleAdrenal MedullaEpinephrine stimulates metabolic activities, bronchial dilation, and blood flow to skeletal muscles and the heartNorepinephrine influences peripheral vasoconstriction and blood pressureFigure 16.16Short-term stressMore prolonged stressStressHypothalamusCRH (corticotropin-releasing hormone)Corticotroph cellsof anterior pituitaryTo target in bloodAdrenal cortex(secretes steroidhormones)GlucocorticoidsMineralocorticoidsACTHCatecholamines(epinephrine andnorepinephrine)Short-term stress response1. Increased heart rate2. Increased blood pressure3. Liver converts glycogen to glucose and releases glucose to blood4. Dilation of bronchioles5. Changes in blood flow patterns leading to decreased digestive system activity and reduced urine output6. Increased metabolic rateLong-term stress response1. Retention of sodium and water by kidneys2. Increased blood volume and blood pressure1. Proteins and fats converted to glucose or broken down for energy2. Increased blood glucose3. Suppression of immune systemAdrenal medulla(secretes amino acid-based hormones)PreganglionicsympatheticfibersSpinal cordNerve impulsesPineal GlandSmall gland hanging from the roof of the third ventricle Pinealocytes secrete melatonin, derived from serotoninMelatonin may affectTiming of sexual maturation and pubertyDay/night cyclesPhysiological processes that show rhythmic variations (body temperature, sleep, appetite)PancreasTriangular gland behind the stomachHas both exocrine and endocrine cellsAcinar cells (exocrine) produce an enzyme-rich juice for digestionPancreatic islets (islets of Langerhans) contain endocrine cellsAlpha () cells produce glucagon (a hyperglycemic hormone)Beta () cells produce insulin (a hypoglycemic hormone)Figure 16.17Pancreaticislet (ofLangerhans)• (Glucagon- producing) cells• (Insulin- producing) cellsPancreaticacinarcells (exocrine)GlucagonMajor target is the liver, where it promotesGlycogenolysis—breakdown of glycogen to glucoseGluconeogenesis—synthesis of glucose from lactic acid and noncarbohydratesRelease of glucose to the blood InsulinEffects of insulinLowers blood glucose levelsEnhances membrane transport of glucose into fat and muscle cellsParticipates in neuronal development and learning and memoryInhibits glycogenolysis and gluconeogenesisInsulin Action on CellsActivates a tyrosine kinase enzyme receptorCascade leads to increased glucose uptake and enzymatic activities thatCatalyze the oxidation of glucose for ATP productionPolymerize glucose to form glycogenConvert glucose to fat (particularly in adipose tissue)Figure 16.18LiverLiverTissue cellsStimulates glucose uptake by cellsStimulatesglycogenformationPancreasPancreasInsulinBloodglucosefalls tonormalrange.StimulatesglycogenbreakdownBloodglucoserises tonormalrange.GlucagonStimulus Bloodglucose levelStimulus Bloodglucose levelGlycogenGlucoseGlycogenGlucoseHomeostatic Imbalances of InsulinDiabetes mellitus (DM)Due to hyposecretion or hypoactivity of insulinThree cardinal signs of DMPolyuria—huge urine outputPolydipsia—excessive thirstPolyphagia—excessive hunger and food consumptionHyperinsulinism:Excessive insulin secretion; results in hypoglycemia, disorientation, unconsciousnessTable 16.4Ovaries and PlacentaGonads produce steroid sex hormonesOvaries produce estrogens and progesterone responsible for:Maturation of female reproductive organsAppearance of female secondary sexual characteristics Breast development and cyclic changes in the uterine mucosaThe placenta secretes estrogens, progesterone, and human chorionic gonadotropin (hCG)Testes Testes produce testosterone thatInitiates maturation of male reproductive organsCauses appearance of male secondary sexual characteristics and sex driveIs necessary for normal sperm productionMaintains reproductive organs in their functional stateOther Hormone-Producing StructuresHeartAtrial natriuretic peptide (ANP) reduces blood pressure, blood volume, and blood Na+ concentrationGastrointestinal tract enteroendocrine cellsGastrin stimulates release of HClSecretin stimulates liver and pancreasCholecystokinin stimulates pancreas, gallbladder, and hepatopancreatic sphincterOther Hormone-Producing StructuresKidneysErythropoietin signals production of red blood cellsRenin initiates the renin-angiotensin mechanismSkinCholecalciferol, the precursor of vitamin DAdipose tissueLeptin is involved in appetite control, and stimulates increased energy expenditureOther Hormone-Producing StructuresSkeleton (osteoblasts)Osteocalcin prods pancreatic beta cells to divide and secrete more insulin, improving glucose handling and reducing body fatThymusThymulin, thymopoietins, and thymosins are involved in normal the development of the T lymphocytes in the immune response Developmental Aspects Hormone-producing glands arise from all three germ layers Exposure to pesticides, industrial chemicals, arsenic, dioxin, and soil and water pollutants disrupts hormone functionSex hormones, thyroid hormone, and glucocorticoids are vulnerable to the effects of pollutantsInterference with glucocorticoids may help explain high cancer rates in certain areasDevelopmental AspectsOvaries undergo significant changes with age and become unresponsive to gonadotropins; problems associated with estrogen deficiency begin to occurTestosterone also diminishes with age, but effect is not usually seen until very old ageDevelopmental AspectsGH levels decline with age and this accounts for muscle atrophy with ageTH declines with age, contributing to lower basal metabolic ratesPTH levels remain fairly constant with age, but lack of estrogen in older women makes them more vulnerable to bone-demineralizing effects of PTH