Endocrine Glands and Hormones 1 - Dr-Sanchezdr- Glands and Hormones. 2 Endocrine Glands Are ductless and secrete hormonesinto bloodstream
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1CHAPTER 11Endocrine SystemChapter 11 OutlineEndocrine Glands and HormonesMechanisms of Hormone ActionPituitary GlandAdrenal GlandsThyroid and Parathyroid HormonesPancreas and Other Endocrine GlandsAutocrine and Paracrine RegulationEndocrine Glands and HHormones2Endocrine GlandsAre ductless and secrete hormones into bloodstreamHormones travel to target cells that contain receptor proteins for itNeurohormones areNeurohormones are secreted into blood by specialized neurons Hormones affect metabolism of targetsChemical Classification of HHormonesChemical Classification of HormonesAmine hormones are derived from tyrosine or tryptophanInclude NE, Epi, thyroxine, melatoninPeptide hormonesPolypeptide and protein hormones are chains of amino acidsInclude ADH, GH, insulin, oxytocin, glucagon, ACTH, PTHGlycoproteins include LH, FSH, TSHSteroids are lipids derived from cholesterol Include testosterone, estrogen, progesterone, alsoterone and cortisol3Hormonal Actions and I t tiInteractionsCommon Aspects of Neural and Endocrine RegulationBoth NS and endocrine system use chemicals to communicate Difference between NTs and hormones is transport in blood and more diversity of effects in hormone targetsSome chemicals are used as hormones and NTsTargets for both NTs and hormones must have specific receptor proteinsMust be a way to rapidly inactivate bothA tissue usually responds to various of hormones 2 hormones are synergistic if work together to produce an effect (additive or complentry)Produce a larger effect together than individual effects added togetherA hormone has permissive effect if it enhancesHormone InteractionsA hormone has permissive effect if it enhances responsiveness of a target organ to 2nd hormoneIf action of 1 hormone inhibits effect of another, it is antagonistic4Hormone Levels and Tissue ResponsesHalf-life is time required for blood level to be reduced by halfRanges from mins to hrs for most (days for thyroid hormones)Normal tissue responses are produced only when hormones are in physiological rangehormones are in physiological rangeHigh (pharmacological) doses can cause a number of side effectsProbably by binding to receptors of different but closely related other hormones Priming effect (upregulation) occurs when a hormone induces more of its own receptors in target cellsResults in greater response in target cellDesensitization (downregulation) occurs after long exposure to high levels of hormoneSubsequent exposure to this hormone produces a Hormone Levels and Tissue Responses q p plesser responseDue to decrease in number of receptors on targetsMost peptide hormones have pulsatile secretion which prevents downregulationMechanisms of Hormone Action5Mechanisms of Hormone ActionTarget cell receptors show specificity, high affinity, and low capacity for a hormoneLipophilic hormones have receptors in target's cytoplasm and/or nucleus because can diffuse thru plasma membraneTheir target is the nucleus where they affect t i titranscriptionCalled genomic action and takes at least 30 minsHydrophilic hormones have receptors on surface of target cellThese act through 2nd messengers; effects are quickSome steroids also act on cell surface receptorsCalled nongenomic actionHormone Effects on Gene ActivityHormones That Bind to Nuclear Receptor ProteinsLipid hormones travel in blood attached to carrier proteinsThey dissociate from carriers to pass thru plasma membrane of targetgReceptors are called nuclear hormone receptors6Nuclear Hormone ReceptorsServe as transcription factors when bound to hormone ligandsActivate transcriptionConstitute a "superfamily" composed of steroid family and thyroid hormone family (which includes vitamin D y y (and retinoic acid)Nuclear Hormone ReceptorsHave ligand (hormone)-binding and DNA-binding domainsBinds hormone and translocates to nucleusBinds to hormone-response element (HRE) on DNA located adjacent to target gene Mechanisms of Steroid HormonesHRE consists of 2 half-sites2 ligand-bound receptors have to bind to each HRE (dimerization) This stimulates transcription of targettranscription of target gene7Mechanism of Thyroid Hormone ActionThyroid secretes 90% T4 (thyroxine) and 10% T399.96% of T4 in blood is bound to carrier protein (thyroid binding globulin - TBG)Only free thyroxine and T3 can enter cells Protein bound thyroxine serves as a reservoirT converted to T inside target cellT4 converted to T3 inside target cellT3 binds to receptor protein located in nucleusMechanism of Thyroid Hormone ActionThe receptor for T3:T3 and receptor bind to 1 half-site Other half-site binds retinoic acidTwo partners form heterodimer that activates HREStimulates transcription of target gene8Hormones That Use 2nd MessengersWater soluble hormones use cell surface receptors because cannot pass through plasma membrane Actions are mediated by 2nd messengers Hormone is extracellular signal; 2nd messenger carries signal from receptor to inside of cellcAMP mediates effects of many polypeptide and glycoprotein hormonesHormone binds to receptor causing dissociation of a G-protein subunitAdenylate Cyclase-cAMPG-protein subunit binds to and activates adenylate cyclaseWhich converts ATP into cAMPcAMP attaches to inhibitory subunit of protein kinaseAdenylate Cyclase-cAMP9 Inhibitory subunit dissociates, activating protein kinase Which phosphorylates enzymes that produce hormones effects cAMP inactivated by phosphodiesteraseAdenylate Cyclase-cAMPServes as 2nd messenger system for some hormonesHormone binds to surface receptor, activates G-protein, which activates phospholipase CPhospholipase-C-Ca2+Phospholipase C splits a membrane phospholipid into 2nd messengers IP3 and DAGIP3 diffuses through cytoplasm to ER Causing Ca2+ channels to openPhospholipase-C-Ca2+10Phospholipase-C-Ca2+Ca2+ diffuses into cytoplasm and binds to and activates calmodulinCa2+-Calmodulin activates protein kinases which phosphorylate enzymes that produce hormone's effectsEpinephrine Can Act Via Two 2ndMessengers Tyrosine Kinase 2nd Messenger System Is used by insulin and many growth factors to cause cellular effectsSurface receptor is tyrosine kinasetyrosine kinaseConsists of 2 units that form active dimer when insulin binds 11Tyrosine Kinase 2nd Messenger SystemActivated tyrosine kinase phosphorylates signaling molecules th t i dthat induce hormone/growth factor effectsInsulin Action Insulin stimulates glucose uptake by means of GLUT 4 carrier proteins2nd messengers gcause vesicles containing GLUT4 transporters to be inserted into plasma membranePituitary Gland12Pituitary Gland Pituitary gland is located beneath hypothalamus at base of forebrainPituitary Gland Is structurally and functionally divided into anterior and posterior lobesHangs below hypothalamus by infundibulumAnterior produces own hormonesControlled by hypothalamusPosterior stores and releases hormones made in hypothalamusPosterior PituitaryStores and releases the hormones vasopressin (ADH)and oxytocin that are made in the hypothalamus13Anterior PituitarySecretes 6 trophichormones that maintain size of targetsHigh blood levelscause target to hypertrophyhypertrophyLow blood levelscause atrophyAnterior PituitaryGrowth hormone (GH) promotes growth, protein synthesis, and movement of amino acids into cellsThyroid stimulating hormone (TSH) stimulates thyroid to produce and secrete T4 and T3Adrenocorticotrophic hormone (ACTH) stimulates adrenal cortex to secrete cortisol aldosteroneadrenal cortex to secrete cortisol, aldosteroneFollicle stimulating hormone (FSH) stimulates growth of ovarian follicles and sperm productionLuteinizing hormone (LH) causes ovulation and secretion of testosterone in testesProlactin (PRL) stimulates milk production by mammary glands 14Anterior PituitaryRelease of Anterior Pituitary hormones is controlled by hypothalamic releasing factorsinhibiting factorsfeedback from levels of target gland hormonesg gAnterior PituitaryReleasing and inhibiting hormones from hypothalamus are released from axon endings into capillary bed in median eminenceCarried by hypothalamo-Carried by hypothalamohypophyseal portal system directly to another capillary bed in A. Pit.Diffuse into A. Pit. and regulate secretion of its hormones15Feedback Control of Anterior Pituitary The hypothalamic-pituitary-gonad axis (control system) Involves short feedback loop in which retrograde flow of blood and hormones from A. Pit. to hypothalamus inhibits secretion of releasing hormone Involves negative feedback of target gland hormones And during menstrual cycle, estrogen stimulates LH surge by positive feedbackSex and Reproductive HormonesGonads (testes and ovaries) secrete steroid hormones testosterone, estrogen, and progesteronePlacenta secretes estrogen, progesterone, hCG, and somatomammotropinThe Ovarian Cycle 3 phasesFollicular Phase - first of ovarian cycleFollicle developmentOvulation Midpoint of ovarion cycleOocyte exits from one ovaryEnters the peritoneal cavity Is swept into the uterine tubeLuteal Phase second of ovarian cycleRemaining follicle becomes a corpus luteum Secretes progesteroneActs to prepare for implantation of an embryo16Ovarian Cycle SummaryThe Uterine CycleSeries of cyclic phases of the endometriumPhases coordinate with the ovarian cycleEndometrial phases directed by FSH and LHPhases of uterine cycle 3 phasesMenstrual phase days 1-5 Stratum functionalis is shedStratum functionalis is shedProliferative phase days 6-14 Secretory phase days 15-28MenstrualphaseMenstrualflowEndometrialglandsBlood vesselsFunctionallayerBasal layerProliferativephaseSecretoryphase1 5 10 15 20 25Days 28Figure 25.18c, dMenstrual and Ovarian Cycles17Higher Brain Function and Anterior Pituitary SecretionHypothalamus receives input from higher brain centers that can affect Anterior Pituitary secretione.g. emotional states and psychological stress can affect circadian rhythms, menstrual cycle, and adrenal hormonesPosterior PituitaryStores and releases 2 hormones produced in hypothalamus:Antidiuretic hormone (ADH/vasopressin)Promotes H2O conservation by kidneysOxytocinStimulates contractions of uterus duringStimulates contractions of uterus during parturitionStimulates contractions of mammary gland alveoli for milk-ejection reflexHypothalamic Control of Posterior PituitarySupraoptic nuclei of hypothalamus produce ADHParaventricular nucleiproduce oxytocinBoth transported along hypothalamo-h h l t t thypophyseal tract to posterior pituitaryRelease controlled in hypothalamus by neuroendocrine reflexes18Adrenal GlandAdrenal GlandsSit on top of kidneysEach consists of outer cortex and inner medullaWhich arise differently during developmentduring developmentAdrenal GlandsMedulla synthesizes and secretes 80% Epinephrine and 20% NorepinephrineControlled by sympathetic division of ANSCortex is controlled by ACTH and secretes:Cortisol which inhibits glucose utilization and stimulates gluconeogenesisstimulates gluconeogenesisAldosterone which stimulate kidneys to reabsorb Na+ and secrete K+And some supplementary sex steroids19Adrenal MedullaHormonal effects of Epinephrine last 10X longer than NorepinephrineInnervated by preganglionic Sympathetic fibersActivated during "fight or flight" responseCauses:I d iIncreased respiratory rate Increased HR and cardiac outputGeneral vasoconstriction which increases venous returnGlycogenolysis and lipolysisStress and the Adrenal GlandStress induces a non-specific response called general adaptation syndrome(GAS)C ACTH dCauses ACTH and cortisol releaseStress and the Adrenal GlandChronic stress can induce high levels of cortisol that cause a number of negative effects:atrophy of hippocampus (involved in memory)reduced sensitivity of tissues to insulin (insulin resistance)i hibiti f ti itinhibition of vagus nerve activitysuppression of growth hormone, thyroid hormone, and gonadotropins20Thyroid GlandThyroid GlandIs located just below the larynxSecretes T4 and T3 which set Base Metabolic Rate(BMR) and are needed for growth, developmentgrowth, developmentA scan of the thyroid 24 hrs. after intake of radioactive iodine (b)Thyroid GlandConsists of microscopic thyroid folliclesOuter layer is follicle cells that synthesize T4Interior filled with colloid, a protein-rich fluid21Production of Thyroid Hormones Iodide (I-) in blood is actively transported into follicles and secreted into colloidWhere it is oxidized to iodine (I2) and attached toiodine (I2) and attached to tyrosines of thyroglobulinA large storage molecule for T4 and T3TSH stimulates hydrolysis of T4 and T3s from thyroglobulin and then secretion Diseases of the Thyroid - Goiter In absence of sufficient dietary iodide, T4 and T3 cannot be made and levels are lowLow T4 and T3 dont provide negativeprovide negative feedback and TSH levels go upBecause TSH is a trophic hormone, thyroid gland growsResulting in a goiter22Hypothyroid - People with inadequate T4 and T3 levels Have low BMR, weight gain, lethargy, cold intoleranceHyperthyroid People with increased T4 and T3 levels.Characterized by weight loss, heat intolerance, Diseases of the Thyroidirritability, high BMR, exopthalmos.Goiter Enlargement of thyroid gland due to iodine deficiencyGrave's diseaseAutoimmune disease where tib di t lik TSH dDiseases of the Thyroidantibodies act like TSH and stimulate thyroid gland to grow and oversecrete.Parathyroid GlandsAre 4 glands embedded in lateral lobes of post. side of thyroid glandSecrete Parathyroid hormone (PTH) ( )Most important hormone for control of blood Ca2+ levels23Parathyroid HormoneRelease stimulated by decreased blood Ca2+Acts on bones, kidney, and intestines to increaseand intestines to increase blood Ca2+ levelsIslets of LangerhansIslets of LangerhansAre scattered clusters of endocrine cells in pancreasContain alpha and beta cells24Alpha cells secrete glucagon in response to low blood glucoseStimulates glycogenolysis and lipolysisIncreases blood glucoseIslets of LangerhansBeta cells secrete insulinin response to high blood glucosePromotes entry of l i t llIslets of Langerhansglucose into cellsAnd conversion of glucose into glycogen and fatDecreases blood glucose
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