Roles for Hedgehog signaling in androgen production and prostate ductal morphogenesis

摘要

PreviousstudieshavedemonstratedthattheHedgehog(Hh)signalingpathwayplaysacriticalroleinthedevelopmentandpatterningofmanyendodermallyderivedtissues.WehaveinvestigatedtheroleofemSonichedgehog/em(emShh/em)informationoftheprostateglandbyexaminingtheurogenitalphenotypeofemShh/emmutantfetuses.ConsistentwithearlierworkreportinganessentialroleforemShh/eminprostateinduction,wehavefoundthatemShh/emmutantfetusesdisplayabnormalurogenitaldevelopmentandfailtoformprostatebuds.Unexpectedly,however,wehavediscoveredthatthisprostatedefectcouldberescuedbythreedifferentmethods:renalgrafting,explantcultureinthepresenceofandrogens,andadministrationofdihydrotestosterone(DHT)topregnantmice,indicatingthattheprostatedefectinemShh/emmutantsisduetoinsufficientlevelsofandrogens.Furthermore,wefindthattheinhibitionofHhpathwaysignalingbytreatmentwithcyclopaminedoesnotblockprostateformationinexplantculture,butinsteadproducesmorphologicaldefectsconsistentwitharoleforHhsignalinginductalpatterning.Takentogether,ourstudiesindicatethattheinitialorganogenesisoftheprostateproceedsindependentlyofShh,butthatShhorotherHhligandsmayplayaroleinsubsequenteventsthatpatterntheprostate./p/div