《药理学》课程PPT教学课件（Endocrine Sys）34 adrenocortical hormones

AdrenocorticalHormones

Adrenocortical Hormones

IntroductionsteroidsAdrenocorticalhormonesareadrenal cortex.The secretionsecreted fromisofcontrolledby the pituitaryreleasecorticotropin (ACTH) and renin-angiotensin-system (RAS)

Introduction Adrenocortical hormones are steroids secreted from adrenal cortex. The secretion is controlled by the pituitary release of corticotropin (ACTH) and renin-angiotensin￾system (RAS)

ClassificationGlucocorticoids(fromzonafasciculata)-cortisone,hydrocortisoneMineralocorticoids(fromzonaglomerulosa)--aldosterone,desoxycorticosteroneSexhormones (fromzona reticularis)福androgen

Classification ➢ Glucocorticoids (from zona fasciculata) - cortisone, hydrocortisone ➢ Mineralocorticoids (from zona glomerulosa) - aldosterone, desoxycorticosterone ➢ Sex hormones (from zona reticularis) - androgen

HypothalamusstressCorticotropinreleasingfactorAnteriorpituitaryCorticotropin(ACTH)zonaAidosteroneglomerulosaZonaCortisolfasciculataZonaAndrogensreticularisAdrenalmedulla

SecretedRateandBloodConcentrationof TypicalAdrenocorticalHormonesAldosteroneHydrocortisone10 mg/d0.125 mg/dSecretedrate at normal conditionPeripheral plasma concentration8AM16 μg/100ml0.1 μg/100ml4 PM4 μg/100ml0.1μg/100ml

Secreted Rate and Blood Concentration of Typical Adrenocortical Hormones Hydrocortisone Aldosterone Secreted rate at normal condition 10 mg/d 0.125 mg/d Peripheral plasma concentration 8 AM 16 μg/100ml 0.1 μg/100ml 4 PM 4 μg/100ml 0.1 μg/100ml

Chemical StructureThe basic structures of adrenocorticalhormonesare steroids,which consistof fourrings: A, B, C and D.The ketonegroup at C3,doublebondsbetween C4 and Cs as well as the carbonylgroup at C2oareessential groups to maintainthebiological activity

Chemical Structure The basic structures of adrenocortical hormones are steroids, which consist of four rings: A, B, C and D. The ketone group at C3 , double bonds between C4 and C5 as well as the carbonyl group at C20 are essential groups to maintain the biological activity

ChemicalStructuresofSeveralAdrenocorticalHormones21CHOHCH2OH20 CO20C0H3C18OHOHD1619LeH3Chydrocortisonedesoxycorticosterone

Chemical Structures of Several Adrenocortical Hormones desoxycorticosterone hydrocortisone

ChemicalStructuresofSeveralAdrenocorticalHormonesCH,OHHOCH,OHC=0HCH3COHHOHH3CHHaldosteroneprednisolone

Chemical Structures of Several Adrenocortical Hormones aldosterone prednisolone

GlucocorticoidsPharmacokinetics·Rapid absorptionafteroral,intramuscularorintravenousadministration.1-2hoursofpeaktimeand8~12hoursofduration·80%withofbindingcirculatinghormonescorticosteroid bindingglobulin(CBG),10%bindingwithalbuminand10%free

Glucocorticoids Pharmacokinetics • Rapid absorption after oral, intramuscular or intravenous administration • 1~2 hours of peak time and 8~12 hours of duration • 80% of circulating hormones binding with corticosteroid binding globulin (CBG), 10% binding with albumin and 10% free

GlucocorticoidsPharmacokineticsInactivation in liver by reduction of double bondsbetweenC4andCsofringAMostmetabolitesexcretedinurine

Glucocorticoids Pharmacokinetics • Inactivation in liver by reduction of double bonds between C4 and C5 of ring A • Most metabolites excreted in urine