Role of glucocorticoids in expression of the adrenergic phenotype in rat embryonic adrenal gland☆

[摘要] Differentiationofthenoradrenergicandadrenergicphenotypeswasdocumentedinratembryonicadrenalchromaffincellsinvivofrom12.5daysofgestation(E12.5)toterm.Theinitialappearanceofthreeenzymesinthecatecholaminergicpathway,tyrosinehydroxylase(T-OH),dopamine-β-hydroxylase(DBH),andphenylethanolamine-N-methyltransferase(PNMT)aswellasendogenouscatecholamines(CA),wasfollowedbyimmunohistochemistryandhistofluorescence.T-OHandDBH,wereemployedasindicesofnoradrenergicexpression,whereasPNMT,theepinephrine-synthesizingenzyme,wasusedasanindexofadrenergicexpression.AtE12.5,T-OH,DBH,andCAwerepresentincellsofthesympatheticgangliaattheleveloftheadrenalanlage.By13.5days,cellscontainingT-OH,DBH,andCA,wereobservedbetweenthesympatheticgangliaanddevelopingadrenal,andwithintheadrenalitself.WhileT-OH,DBH,andCAwerepresentinadrenalmedullarycellsfromtheearlieststagesofadrenaldevelopment,PNMT,incontrast,wasundetectableinganglionprimordia,migratingcells,orwithintheadrenalbefore17days.PNMTinitiallyappearedatE17insmallclustersofcellsscatteredthroughouttheadrenal.ThenumberofcellscontainingPNMTandtheintensityofstainingincreaseddramaticallyfromE17toterm.Anumberofexperimentalmanipulationswereemployedinvivotoinvestigatetheroleofglucocorticoidsindifferentiationoftheadrenergicphenotype.Chronicoracutetreatmentofmothersand/orembryoswithvariousglucocorticoids,adrenocorticotrophichormone(ACTH),orS-adenosylmethionine(SAM)didnotresultinprecociousappearanceofPNMT.Moreover,theinitialexpressionofPNMTwasnotpreventedordelayedbyembryonichypophysectomyorbytreatmentwithinhibitorsofadrenocorticalfunction.Consequently,theinitialexpressionofPNMTonE17.0isnotdependentonnormalglucocorticoidlevels,cannotbeinducedprematurelybyglucocorticoids,andisindependentofthepituitary-adrenalaxis.However,theontogeneticincreaseinPNMTlevelsafterinitialexpressionhasoccurreddoesrequireintactpituitary-adrenalfunction.Ourobservationssuggestthatdifferentmechanismsregulateinitialexpressionandsubsequentmodulationofneurotransmitterphenotype.

[学科分类] 生物科学（综合）