Androgen Resistance in Squirrel Monkeys (Saimiri spp.)

摘要

Thegoalofthisstudywastounderstandthebasisforhighandrogenlevelsinsquirrelmonkeys(Saimirispp.).Massspectrometrywasusedtoanalyzeserumtestosterone,androstenedione,anddihydrotestosteroneofmalesquirrelmonkeysduringthenonbreeding(n=7)andbreeding(n=10)seasons.Allhormonelevelswereelevatedcomparedwiththoseofhumans,evenduringthenonbreedingseason;thehighestlevelsoccurredduringthebreedingseason.Theratiooftestosteronetodihydrotestosteroneinsquirrelmonkeysishighduringthebreedingseasoncomparedtoman.Squirrelmonkeysmayhavehightestosteronetocompensateforinefficientmetabolismtodihydrotestosterone.Wealsoinvestigatedwhethersquirrelmonkeyshavehighandrogenstocompensateforlow-activityandrogenreceptors(AR).TheresponsetodihydrotestosteroneinsquirrelmonkeycellstransfectedwithARandAR-responsivereporterplasmidswas4-fold,comparedwith28-foldinhumancells.ThisresultwasnotduetooverexpressionofcellularFKBP51,whichcausesglucocorticoidandprogestinresistanceinsquirrelmonkeys,becauseoverexpressionofFKBP51hadnoeffectondihydrotestosterone-stimulatedreporteractivityinahumanfibroblastcellline.TotestwhethertheinherentlylowlevelsofFKBP52insquirrelmonkeyscontributetoandrogeninsensitivity,squirrelmonkeycellsweretransfectedwithanARexpressionplasmid,anAR-responsivereporterplasmid,andaplasmidexpressingFKBP52.ExpressionofFKBP52decreasedtheECsubxmlns="http://pub2web.metastore.ingenta.coms/"50/suborincreasedthemaximalresponsetodihydrotestosterone.Therefore,thehighandrogenlevelsinsquirrelmonkeyslikelycompensatefortheirrelativelylow5#945;-reductaseactivityduringthebreedingseasonandARinsensitivityresultingfromlowcellularlevelsofFKBP52.