生理學(xué)內(nèi)分泌- 2013

第十一章內(nèi)分泌ENDOCRINE神經(jīng)遞質(zhì)內(nèi)分泌激素神經(jīng)內(nèi)分泌激素旁分泌自分泌細(xì)胞因子化學(xué)信使與機(jī)體功能協(xié)調(diào)Whatarehormones?WhatisEndocrinology?ReviewmajorendocrineglandsWhatphysiologicalprocessesarecontrolledbyhormones?內(nèi)分泌系統(tǒng)內(nèi)分泌腺體

散在的內(nèi)分泌細(xì)胞（甲狀腺、腎上腺…）（心房肌細(xì)胞、腎球旁細(xì)胞…）第一節(jié)概述

一、體內(nèi)重要的內(nèi)分泌腺及其所分泌的激素

垂體(pituitary)(前葉)腺垂體(adenohypophysis):

PRL、GH、MSH、LH、FSH、TSH、ACTH

甲狀腺合成T3、T4（后葉）神經(jīng)垂體（neurohypophysis)：ADH、OXT甲狀旁腺：甲狀旁腺素PTHC細(xì)胞：CalcitoninCalcitonin(降鈣素):

甲狀腺濾泡旁細(xì)胞(ClearCell,C細(xì)胞)

Effects：

血Ca2+及血磷（直接抑制破骨細(xì)胞的活性，增加尿Ca2+、P的排出）

調(diào)節(jié)血Ca2+

水平速度最快神經(jīng)組織(少量)外周神經(jīng)軸突釋放CGRP

(calcitonin-gene-relatedpeptides,CGRP)3Parathyroidgland:

甲狀旁腺激素（Parathyroidhormone,PTH）Effects：血Ca2+、血PMechanism：＊骨Ca2+

的釋放

＊腎遠(yuǎn)球小管對(duì)Ca2+

的重吸收腎近球小管對(duì)P的重吸收＊VitD325-羥化酶25(OH)VitD3

PTH激活1－羥化酶1,25(OH)2VitD3（促進(jìn)腸道吸收鈣）PTH過高，甲狀旁腺功能亢進(jìn)：腎結(jié)石、胃潰瘍PTH過少：低血鈣（神經(jīng)－肌肉，心臟）骨鈣素(osteocalcin，49AA)(-羧基谷氨酸蛋白或谷依賴VitK蛋白）由成骨細(xì)胞合成并分泌到骨基質(zhì)中，是骨基質(zhì)中含量最豐富的非膠原蛋白，能與鈣結(jié)合。

作用：調(diào)節(jié)和維持骨鈣參與調(diào)節(jié)鈣、磷的有：calcitonin、PTH、1,25(OH)2VitD3、osteocalcin4胰島(pancreaticislet)A細(xì)胞：20％分泌胰高血糖素(glucagon)Effect：升高血糖

Mechanism：*增加肝內(nèi)糖原分解1molglucagon使糖原釋放3,000,000molglucose)

*增加糖異生B細(xì)胞：60~70%分泌胰島素(insulin)Effect：降低血糖，促進(jìn)合成代謝Questions:糖尿病人尿量有何改變，Why？

胰島大部分切除的病人，尿量有何改變，Why？

靜脈注射20％Glucose，尿量有何改變，Why？ClassicHormonewithMultipleControlsExample:InsulinPancreas

Enteroglucagonssecretedbyendocrinecellsinthesmallintestine

Regulation:代謝水平（血糖，精氨酸、賴氨酸）(口服氨基酸查血中胰島素水平，胰島B細(xì)胞功能檢測(cè)指標(biāo)）神經(jīng)調(diào)節(jié)：迷走N促進(jìn)（ACh，胃腸激素）交感N抑制（NE）其它激素的調(diào)節(jié)：促胃液素、胰泌素、CCK、抑胃肽直接促 insulin分泌生長激素、皮質(zhì)醇等因升糖間接促insulin 分泌5.腎上腺（adrenalgland)

髓質(zhì)：Adr，NE，腎上腺髓質(zhì)素皮質(zhì)：cortisol，ADS，sexualhormone6.性腺（gonad)

睪丸(testis)

卵巢（ovary)7.胎盤(placenta)散在的內(nèi)分泌細(xì)胞：胃腸激素、EPO、心房利尿肽一、激素（Hormone）由內(nèi)分泌腺或散在的內(nèi)分泌細(xì)胞分泌的高效能的生物活性物質(zhì)。經(jīng)組織液或血液傳遞而發(fā)揮其調(diào)節(jié)作用。激素的釋放周期性、階段性激素的運(yùn)輸結(jié)合型游離型一、激素（Hormone）定義圖11-1激素的遞送方式TelecrineParacrineAutocrineNeurocrine激素的遞送方式激素的代謝

半衰期（halflife）激素活性在血液中消失一半的時(shí)間1、調(diào)節(jié)新陳代謝2、調(diào)節(jié)生長發(fā)育3、與神經(jīng)系統(tǒng)配合，增強(qiáng)適應(yīng)能力激素的作用：激素的分類含氮激素類固醇（甾體激素）固醇類激素第三類激素肽類蛋白質(zhì)激素胺類激素NE、Adr、甲狀腺激素腎上腺皮質(zhì)激素、性腺激素1,25-二羥維生素D3前列腺素（脂肪酸衍生物）ClassificationofHormones3maintypesofhormonesPeptidesandproteinsSteroidsAminesDifferonbasisofsynthesis,storage,release,transportandcellularmechanismofactionRangefrom3aminoacidstohundredsofaminoacidsinsize.Oftenproducedaslargermolecularweightprecursorsthatareproteolyticallycleavedtotheactiveformofthehormone.Peptide/proteinhormonesarewatersoluble.Comprisethelargestnumberofhormones–perhapsinthousandsPeptide/proteinhormonesAreencodedbyaspecificgenewhichistranscribedintomRNAandtranslatedintoaproteinprecursorcalledapreprohormonePreprohormonesareoftenpost-translationallymodifiedintheERtocontaincarbohydrates(glycosylation)Preprohormonescontainsignalpeptides(hydrophobicaminoacids)whichtargetsthemtothegolgiwheresignalsequenceisremovedtoformprohormoneProhormoneisprocessedintoactivehormoneandpackagedintosecretoryvessiclesPeptide/proteinhormonesSecretoryvesiclesmovetoplasmamembranewheretheyawaitasignal.ThentheyareexocytosedandsecretedintobloodstreamInsomecasestheprohormoneissecretedandconvertedintheextracellularfluidintotheactivehormone:anexampleisangiotensinissecretedbyliverandconvertedintoactiveformbyenzymessecretedbykidneyandlungPeptide/proteinhormonesPeptide/proteinhormonesynthesisProcessinginroughER(lossofsignalpeptide)Pro-vasopressin-lys-arg--lys-arg--COOHH2N-SignalpeptidePrepro-vasopressin-lys-arg--lys-arg--COOHH2N-VasopressinNeurophysinIIADHcarrierproteininaxonGlycoproteinProcessinginGolgi–hydrolysisoflys-argbondsProcessingofprepro-vasopressin.H2N-H2N-H2N-Allsteroidhormonesarederivedfromcholesterolanddifferonlyintheringstructureandsidechainsattachedtoit.Allsteroidhormonesarelipidsoluble類固醇激素糖皮質(zhì)激素Glucocorticoids;cortisolisthemajorrepresentativeinmostmammals鹽皮質(zhì)激素Mineralocorticoids;aldosteronebeingmostprominent雄激素Androgenssuchastestosterone雌激素Estrogens,includingestradiolandestrone孕激素Progestogens(alsoknownaprogestins)suchasprogesterone類固醇激素的類型合成后直接分泌，不進(jìn)行包裝。都自膽固醇Cholesterol衍生而來合成類固醇激素的酶位于線粒體及滑面內(nèi)質(zhì)網(wǎng)都是脂溶性的，故可自由通過漿膜，無需在細(xì)胞內(nèi)儲(chǔ)存類固醇激素特點(diǎn)類固醇激素不溶于水，血液中同特定球蛋白結(jié)合后運(yùn)輸.皮質(zhì)醇結(jié)合球蛋白（Corticosteroidbindingglobulin）

運(yùn)輸皮質(zhì)醇性類固醇結(jié)合球蛋白（Sexsteroidbindingglobulin）運(yùn)輸睪酮和雌二醇carriestestosteroneandestradiolInsomecasesasteroidissecretedbyonecellandisconvertedtotheactivesteroidbythetargetcell:anexampleisandrogenwhichsecretedbythegonadandconvertedintoestrogeninthebrain類固醇激素特點(diǎn)

Eicosanoidsarealargegroupofmoleculesderivedfrompolyunsaturatedfattyacids.Theprincipalgroupsofhormonesofthisclassareprostaglandins,prostacyclins,leukotrienesandthromboxanes.FattyAcidDerivatives－Eicosanoids激素的一般特征1、信息傳遞作用2、相對(duì)特異性3、高效能生物放大作用

(細(xì)胞內(nèi)酶促放大作用)4、相互作用協(xié)同作用拮抗作用允許作用（permissiveaction）下丘腦腺垂體腎上腺CRH0.1ugACTH1ug糖皮質(zhì)激素40ugSynergismCombinedactionofhormonesismorethanjustadditive!Example:Bloodglucoselevels&synergisticeffectsofglucagon,cortisolandepinephrinePermissivenessHormoneAwillnotexertfulleffectwithoutpresenceofhormoneB.Example:Thyroidhormone&growthhormoneHormoneBdiminishestheeffectofhormoneAExample:Glucagon(and?)vs.InsulinHormoneAntagonistsandCancer:TamoxifenAntagonism激素的作用機(jī)制Adr+肝細(xì)胞磷酸化酶活性肝糖元分解1、Adr+肝臟勻漿肝糖元分解

不依賴于完整的細(xì)胞結(jié)構(gòu)2、Adr+磷酸化酶酶的活性不變

說明Adr引起酶活性增高并不是直接作用于該酶，而是與勻漿有關(guān)。3、勻漿高速離心上清液（胞漿）沉淀（細(xì)胞膜碎片）Adr+細(xì)胞膜碎片無效Adr+上清液無效Adr+細(xì)胞膜碎片+上清液有效

說明Adr要引起磷酸酶活性增強(qiáng)，必需依賴于細(xì)胞膜和勻漿同時(shí)存在。

勻漿中cAMP增多4、cAMP+肝細(xì)胞勻漿液產(chǎn)生效應(yīng)

說明Adr首先作用于細(xì)胞膜，產(chǎn)生一系列反應(yīng)，使細(xì)胞生成了cAMP，能激活磷酸化酶，引起相應(yīng)的效應(yīng)。多種第二信使（Ca+、cGMP、前列腺素、IP3…）發(fā)現(xiàn)cAMP與生物效應(yīng)不一致1、激素是第一信使5、逐級(jí)放大過程胰高血糖素（1）AC（1）磷酸化酶（1000）2、與特異性膜受體結(jié)合4、多種第二信使（cAMP、cGMP、Ca2+、IP3、DG…）3、G蛋白的耦聯(lián)作用1.與G蛋白耦聯(lián)細(xì)胞膜受體

膜受體（糖蛋白）細(xì)胞膜外區(qū)段質(zhì)膜部分細(xì)胞內(nèi)區(qū)段糖基識(shí)別部位跨膜α-螺旋G蛋白的耦聯(lián)作用Hs+RsGsα-GTPβγGsα-GTPβγ轉(zhuǎn)變?yōu)榧せ預(yù)CGsα-GDPβγGTP水解再結(jié)合Hi+Riβγ抑制ACGiα-GTPβγGiα-GTPEffectorgb

b[1]Hormonebindstoreceptor;hormone-RcomplexinteractswithG-proteinHormoneReceptoraFigure1.SignaltransductionbyGproteins

[2]

GDPdissociates;GTPreplacesGDPonthe

-subunit;hormonedissociatesGTPGDPGTPGTPGTPGDPGDPGDPEffectorgb

b[1]Hormonebindstoreceptor;hormone-RcomplexinteractswithG-proteinFigure1.SignaltransductionbyGproteins

[2]

GTPdisplacesGDPonthe

-subunithormonedissociatesaGTPaGTPaGTP

aGTP[3]

-subunitdissociatestheninteractswiththeeffector(E)GDPReceptor[4]GTPaseactivityofthe

-subunithydrolyzesGTPaGDPPiPiPiEffectorgb

bReceptorGDPaGDP[4]GTPaseactivityofthe

-subunithydrolyzesGTPPi

aGDP[5]WithoutGTPboundtothe

-subunit,itreassociateswiththe

and

subunitstorestoretheinitialsetup.aGDPaGDPFigure1.SignaltransductionbyGproteins

Adenylylcyclasegb

baGTPaGTP

ATPCyclicAMPinactivecatalyticsubunitsPROTEINKINASEAregulatorysubunitsreassociationphosphorylatesenzymestoregulatemetabolism(e.g.,phosphorylasekinase,glycogensynthase,hormone-sensitivelipase,acetylCoAcarboxylase,HMG-CoAreductase)cyclicAMPadenylylcyclasedissociationATP5’AMPPhosphodiesteraseFigure2.CyclicAMPactivationofproteinkinaseA

activecatalyticsubunitsCYTOPLASMExtracellularSpaceReceptorEndoplasmicReticulum

inositol+3phosphates

Hormone-receptorcomplexinactiveGqGDPactiveGqGTPGDPinactivePLCactivePLC

PIP2DAG

IP3Ca2+Ca2+

IP3CaM-dependentkinaseCellularresponses

GTPdisplacesGDP(seestep2,Fig1)

GTPHormone

inactivePKC

activatedPKC圖11-3磷脂酰肌醇信息傳遞系統(tǒng)示意圖PIP2：磷脂酰二磷肌醇DG：二酰甘油IP3：三磷酸肌醇PKC：蛋白激酶CCaM:鈣調(diào)蛋白激活蛋白激酶C

激活依賴鈣調(diào)蛋白的蛋白激酶

具有酪氨酸蛋白激酶（PTK）活性，與激素結(jié)合后，膜內(nèi)區(qū)段的PTK激活，使自身肽鏈和膜內(nèi)蛋白質(zhì)底物中的酪氨酸殘基發(fā)生磷酸化，誘發(fā)細(xì)胞內(nèi)效應(yīng)。2.酪氨酸蛋白激酶受體3.細(xì)胞膜內(nèi)受體胞漿受體

核受體（核內(nèi)多肽鏈）

胞漿中特殊的可溶性蛋白質(zhì)，能特異性地與相應(yīng)激素結(jié)合，形成復(fù)合物，使激素轉(zhuǎn)移至核內(nèi)發(fā)揮作用。如：糖皮質(zhì)激素受體、性激素受體激素結(jié)合結(jié)構(gòu)域DNA結(jié)合結(jié)構(gòu)域轉(zhuǎn)錄激活結(jié)構(gòu)域掩蔽暴露羧基端氨基端如：甲狀腺激素、1,25-（OH）維生素D3、性激素圖11-4類固醇激素作用機(jī)制示意圖激素受體調(diào)節(jié)對(duì)受體數(shù)量及親和力的調(diào)控與影響。增量調(diào)節(jié)（上調(diào)）受體數(shù)量和親和力增加如：雌激素、糖皮質(zhì)激素減量調(diào)節(jié)（下調(diào)）受體數(shù)量和親和力減少如：胰島素

受體內(nèi)化：受體與其相應(yīng)的激素結(jié)合后，形成的激素-受體復(fù)合物的入胞過程。激素釋放調(diào)節(jié)下丘腦腺垂體靶腺長反饋短反饋超短反饋短反饋“Unbalanceleadstodisease”Dueto:HypersecretionHyposecretionAbnormaltissueresponseEndocrinePathologiesDueto?Iatrogenic________________Symptoms:ExaggeratedEffectsExamples:GravesdiseaseGigantismCushing’sSyndromeHypersecretion:Mostcommoncause:Graves'diseaseAutoantibodies(TSI)bindtoTSHreceptorandstimulatethyroidhormoneproductionThisactivationbyTSIisnotsubjecttothenormalnegativefeedbackloop.Example:HyperthyroidismCharacteristicfeatureofGraves’disease:ExophthalmusHyposecretion:Dueto?Symptoms:NormaleffectsofhormonediminishedorabsentExamples:HypothyroidismDwarfismAddison’sdiseaseMostcommoncauseinUS:

chronicautoimmunethyroiditis(Hashimoto'sthyroiditis)Othercausessurgicalremovalofthethyroidglandradioactiveiodinetreatmentexternalradiationadeficiencyindietaryiodideconsumption(=endemicgoiter)Example:HypothyroidismSymptoms:Duringchildhood:stuntedgrowthretardationlethargylowbodytemp.Inadulthood:weightgainlethargylowbodytemp.Hypothyroidismcont.

Hormonelevelsnormal,targetunresponsiveDueto:Abnormalhormone/receptorinteractioncauses?Abnormalsignaltransductioncauses?AbnormalTissueResponsivenessPrimaryPathologyDefectarisesinlastintegrationcenterinthereflexExamples?SecondaryPathologyDefectarisesinoneofthetrophicintegratingcentersExamples?DiagnosisofEndocrinePathologies第二節(jié)下丘腦和垂體下丘腦神經(jīng)垂體腺垂體門脈系統(tǒng)垂體柄下丘腦的內(nèi)分泌功能1、9種調(diào)節(jié)性多肽3對(duì)3個(gè)2、TRH、GnRH、CRH、GHRH為脈沖式釋放調(diào)節(jié)下丘腦促垂體區(qū)肽能神經(jīng)元活動(dòng)的遞質(zhì)肽類物質(zhì)如：腦啡肽、β-內(nèi)啡肽、P物質(zhì)、蛙皮素單胺類物質(zhì)如：NE、5-HT、DAHypothalamicReleasingHormonesAnteriorpituitaryhormones(GH,TSH,ACTH,

-LTH,

-endorphin,MSH,PRL,FSH,LH)andtheiractionstogetherwithhypothalamicreleasinghormones.Neurotransmitters+/-ReleasingHormonesTRH+CRH+Estrogen+PRIH(dopamine)-GnRH+

ANTERIORPITUITARYHORMONES(HYPOTHALAMUS)GHTSHTHYROIDACTH

-LTHparsintermedia

cells

-ENDORPHIN

-MSHCLIPPRLFSHLHGHRH+GHIH-

Fat,CHOandproteinmetabolismLIVERADRENALCORTEX

-ENDORPHINSKINDARKENING

andCNSFUNCTIONSTESTISOVARYTESTISMAMMARYGLANDTESTISOVARYgrowth,developmentLIVERHYPERGLYCEMICEFFECTS

IGF-ISOMATICCELLGROWTHT4/T3CELLOXIDATIONSGROWTHCORTICOSTEROIDSANALGESIASTRESSADAPTATIONPROTECTIVEEFFECTSLACTATIONandrogenbindingprotein;

inhibinTESTO-STERONEOVARYTESTISOVARYgrowth,development

testosteroneproduction/actionsinterstitialcelldevelopmentovulationTHYROIDGHADRENALCORTEX

-ENDORPHINMAMMARYGLANDTESTISTESTISPROGESTERONECORPUSLUTEUMESTRADIOL

follicledevelopment

seminaltubulegrowthandspermatogenesis作用：TRHGnRHGHRHCRHPRFNEDA5-HT腦啡肽β-內(nèi)啡肽腺垂體

遠(yuǎn)側(cè)部（為主75%）中間部結(jié)節(jié)部

顆粒型細(xì)胞（有內(nèi)分泌功能）

無顆粒型細(xì)胞（無內(nèi)分泌功能）GH細(xì)胞催乳素細(xì)胞促甲狀腺細(xì)胞促腎上腺細(xì)胞促性腺細(xì)胞濾泡星形細(xì)胞未分化細(xì)胞腺垂體釋放的激素生長激素促激素促黑素催乳素促甲狀腺激素（TSH）促腎上腺激素（ACTH）促性腺激素卵泡刺激素（FSH）黃體生成素（LH）生長激素GrowthHormone(GH)正常垂體提取液去垂體?下丘腦神經(jīng)垂體腺垂體門脈系統(tǒng)生長激素結(jié)合蛋白GH-bindingprotein(GHBP)GHGHBP高親和力低親和力61kD100kD主要存在形式巨人癥肢端肥大癥離體培養(yǎng)的軟骨細(xì)胞軟骨無生長軟骨生長GH正常血漿去垂體動(dòng)物的血漿

加GH的去垂體動(dòng)物血漿GH肝生長介素Somatomedin(SM)胰島素樣生長因子SMSM-1SM-270肽GH依賴性

67肽促進(jìn)胎兒生長

生長激素

生長介素軟骨、肌肉等組織蛋白質(zhì)合成Ca2+、Na+、K+等元素儲(chǔ)留

分解脂肪

降低糖利用下丘腦GHRHGHRIH腺垂體GHSM興奮抑制GHRH生長激素釋放激素GHRIH生長激素釋放抑制激素血糖降低慢波睡眠應(yīng)激刺激甲狀腺激素雌激素雄激素覺醒GH的睡眠周期慢波睡眠快波睡眠ZZZGHGH催乳素（Prolactin，PRL）199氨基酸、分子量22000主要作用1、對(duì)乳腺的作用：維持泌乳、促進(jìn)乳腺發(fā)育2、對(duì)性腺的作用：促進(jìn)黃體生成，維持孕激素分泌小劑量PRL：E、P升高大劑量PRL：抑制作用乳腺發(fā)育有關(guān)激素：E,

P,GH,C,Ins,T,PRL3、參與應(yīng)激下丘腦PRFPIF腺垂體PRL興奮抑制PRL分泌調(diào)節(jié)多巴胺雌激素催產(chǎn)素（Oxytocin，OXT）1、對(duì)乳腺的作用：2、對(duì)子宮的作用：參與射乳反射，使乳腺肌上皮收縮，維持哺乳期乳腺不萎縮促妊娠子宮收縮射乳反射第四節(jié)甲狀腺

T4T3日分泌總量96ug/天30ug/天激素含量多（95%）少（5%）生物活性弱（1）強(qiáng)（3-5）起效時(shí)間慢而持久快而迅速半衰期（T1/2）6-8天1-2天更新率10%75%血中形式結(jié)合型為主游離型為主甲狀腺外分布多（900ug）少（40ug）FollicleC-cell(calcitonin)CuboidalepithelialcellsThenumberandpositionofiodinesubstituentsisthemostimportantdeterminantofhormoneactivity.T3andT4arepoorlysolubleinwater;needcarriers.合成貯存釋放運(yùn)輸代謝原料過程聚碘活化碘化耦聯(lián)TransporterIodinationbyTPEndocytosisThyroglobulinProteolysisThyroglobulinsecretionEndothelialcellBloodColloidT3andT4SynthesisandSecretionTPisanintegralmembraneproteinintheapical(colloid-facing)membraneofthefollicleepithelialcells.Thyroidperoxidase(TP)IodinationConjugationTREs:thyroidresponseelementsReceptorbindingdomainisa“zincfinger”Heterodimersarewithretinoicacid(RA)receptorRXRMechanismofActionTRE圖11-9甲狀腺激素合成及代謝示意圖TPO：過氧化酶TG：甲狀球蛋白對(duì)代謝的影響產(chǎn)熱物質(zhì)代謝糖脂肪蛋白質(zhì)對(duì)生長與發(fā)育的影響腦長骨對(duì)神經(jīng)系統(tǒng)的影響其它(心血管、消化…）甲狀腺激素的生物學(xué)作用下丘腦-腺垂體-甲狀腺軸反饋調(diào)節(jié)自身調(diào)節(jié)Wolff-Chaikoff效應(yīng)自主神經(jīng)對(duì)甲狀腺活動(dòng)的影響交感神經(jīng)副交感神經(jīng)甲狀腺功能的調(diào)節(jié)TRH:atripeptideUtilizestheDAG/PKCsignalingStimuli:-ColdanincreaseinTSH-Emotions(stimulationofsympatheticnerves)

anacutedecreaseinTSHThehypothalamic-pituitary-thyroidaxis脈沖式釋放、日周期作用促甲狀腺激素的合成與釋放促葡萄糖氧化，提供過氧化酶所需的還原型輔酶II刺激甲狀腺細(xì)胞增生受下丘腦TRH的調(diào)節(jié)TSH的分泌、功能及調(diào)節(jié)圖11-10甲狀腺激素分泌的調(diào)節(jié)示意圖⊕表示促進(jìn)或刺激⊙表示抑制下丘腦GHRIFTRH腺垂體甲狀腺興奮抑制甲狀腺激素分泌調(diào)節(jié)糖皮質(zhì)激素

GH雌激素甲狀腺激素第六節(jié)腎上腺

TheAdrenalGlandWhenyouthinkabouttheadrenalgland,youshouldthinkaboutstress.AdrenalSteroidhormonesglucocorticoidsandmineralocorticoidsAdrenalmedullaryhormonesCathecholamines:epinephrineandnorepinephrineHistochemistryTheadrenalglandhasaconnectivetissuecapsule,richlyvascularizedandinnervated.Thezonesinthecortex:zonaglomerulosa-thin,outermostzone;zonafasiculata-thick,middlezone;zonareticularis-thin,innerzoneAdrenalglandcathecholamines(mineralocorticoids)TableofadrenalhormonesZonaglomerulosamineralocorticoids(aldosterone)Zonafasiculataglucocorticoids(cortisol)Zonareticularissexsteroids(androgens)MedullaCortexCatecholamines:epinephrineandnorepinephrine圖11-16腎上腺皮質(zhì)激素合成的主要步驟球狀帶束狀帶網(wǎng)狀帶醛固酮皮質(zhì)醇性激素雌激素雄激素圖11-15幾種主要的腎上腺皮質(zhì)激素有化學(xué)結(jié)構(gòu)AdrenalSteroidsCholesterolPregenoloneProgesterone17-hydroxypregnenolone17-hydroxyprogesteroneAldosteroneCortisolAndrogensPhysiologicEffectsofAldosteroneThemainrole:regulationofminerallevels,particularlyNaandKinextracellularfluids.Themajortarget:thedistaltubule(kidney)IncreasedresorptionofNa+ions(Na+lossinurineisreduced)Increasedresorptionofwater,withconsequentexpansionofextracellularvolume.ThisisanosmoticeffectdirectlyrelatedtotheincreasedresorptionofNa.IncreasedexcretionofK+ionsThemolecularactionsofaldosteroneStimulationoftranscriptionofTheNa/KATPaseor“sodiumpump”inthebasolateralmembranesoftubularepithelia.TheNa-channelwhichfacilitatesthereuptakeofNafromthelumen.Themajorneteffect:TheconservationofbodyNaandwater.Electrolyteimbalancescouldresultinhypotensionandcardiacfailure.ControlofAldosteroneSecretionStimulators:K+ionsAngiotensinIISodiumdefficiency

Suppressors:AtrialnaturetichormoneHighNa+;K+deficiencyGlucocorticoids(Cortisol)ThemostfrequentlyprescribedasdrugsPotentanti-inflammatoryandimmunosuppressiveproperties.Themostactive:cortisol(95%)MechanismviasteroidreceptorsTransportinplasma:corticosteroid-bindingglobulin(transcortin)decreasesthemetabolicclearancetheboundsteroidisnotactivepreventsfluctuationsincortisolconcentrationControlofCortisolSecretionStimulator:adrenocorticotropichormone(ACTH)ACTHissecretedundercontrolofthehypothalamicpeptidecorticotropic-releasinghormone(CRH).Virtuallyanytypeofphysicalormentalstressresultsintheelevationofbloodcortisol.theanteriorpituitaryCRHtheadrenalEffectsonMetabolismduringFastingThenameglucocorticoid:“involvedinglucosemetabolism”

Cortisolpreservesglucoseduringfasting Mechanismst