adrenocortical insufficiency - stud：肾上腺皮质功能不全-螺柱

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1、ADRENOCORTICALINSUFFICIENCYTHEADRENALCORTEXBASISCONCEPTSADRENOCORTICALHISTOLOGYTheadrenalcortexiscomposedofthreeconcentriczoneswithdistinctsteroidbiosyntheticcapacities.Zonaglomerulosa–biosynthesisofmineralocorticoidsZonafasciculata–biosynthesisofglucocorticoidsZonareticularis–biosynthesisofadren

2、alandrogens.STEROIDBIOSYNTHESISSteroidogenesisresultsfromspecificsequentialenzymaticconversionsofcholesterolsubstrateintosteroidhormones,whichexertawidevarietyofbiologicalactivities.STEROIDBIOSYNTHESISAseriesofsteroidogenicenzymesarecompartmentalizedeitherinthemitochondriaorintheendoplasticreticulum

3、.SeveraloftheseenzymesbelongtothesuperfamilyofmixedfunctionoxidaseenzymesknownascytochromeP450.STEROIDBIOSYNTHESISApproximately~80%ofadrenalcholesterolsourcesareprovidedbycirculatinglowdensitylipoprotein(LDL).TheadrenalcellscanalsosynthesizecholesteroldenovofromacetylcoenzymeA.STEROIDBIOSYNTHESISThe

4、firstrate-limitingstepinsteroidogenesisinvolvestheremovalofsixcarbonsfromthelateralchainofcholesterolbyintegralinnermitochondrialmembraneP450sidechaincleavage(CYP11A1)enzymetogeneratepregnenolone.NomenclatureforsteroidogenicenzymesnowutilizedTrivialnamePastCurrentCholesterolside-chaincleavageenzyme;

5、desmolaseP450sccCYP11A13β-Hydroxysteroiddehydrogenase3β-HSD3β-HSD17α-Hydroxylase/17,20-lyaseP450c17CYP1721-HydroxylaseP450c21CYP21A211β-HydroxylaseP450c11CYP11B1Aldosteronesynthase;corticosterone18-methylcorticosteroneoxidase/lyaseP450C11ASCYP11B2Mainsteroidbiosyntheticpathways(mineralocorticoidsand

6、glucocorticoids).cholesterolpregnenoloneprogesterone11-deoxycorticosterone(DOC)corticosterone(B)18OH-corticosteroneALDOSTERONE3β-HSDIICYP21A2CYP11B217αOH-pregnenoloneCYP1717α-hydroxylase17,20-lyase17αOH-progesterone11-deoxycortisol(S)CORTISOL(F)CYP11B1ZONAFASTICULATAZONAGLOMERULOSA11β-hydroxylaseCYP

7、11A118-hydroxylase18-methyloxidaseMainsteroidbiosyntheticpathways(adernalandrogens).cholesterolpregnenoloneprogesterone3β-HSDII17αOH-pregnenolone17α-hydroxylase17,20-lyase17αOH-progesteroneZONARETICUL