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Abstract

Müllerian inhibiting substance inhibits testosterone synthesis in adult rats 
Sriraman,Venkataraman; Niu,Enmei; Matias,Jonathan R.; Donahoe,Patricia K.; MacLaughlin,David T.; Hardy,Matthew P.; Lee,Mary M.
Journal of Andrology 22(5): 750-758
Publication date: 2001


Mullerian inhibiting substance (MIS) is a gonadal hormone that causesregression of the Mullerian ducts during male sexual differentiation.Postnatally, MIS inhibits the proliferation and differentiation of immatureLeydig cells, and transgenic mice that overexpress MIS have decreased serumtestosterone concentrations. To elucidate the effects of MIS on androgenregulation in the postnatal testis, we examined testosterone synthesis inadult Sprague-Dawley rats following intratesticular and intraperitonealinjections of MIS. Intratesticular MIS injection achieved high localconcentrations of MIS (574.0 +/- 60.0 ng/mL) at 4 hours, with acorresponding decline in serum testosterone concentrations to 0.7 +/- 0.1ng/mL, compared to 1.1 +/- 0.2 ng/mL with intraperitoneal MIS and 1.6 +/-0.1 ng/mL with intratesticular vehicle (IT-Veh) (P < .001).Intratesticular administration of MIS (IT-MIS) resulted in much higherserum and testicular interstitial fluid MIS concentrations than theintraperitoneal route. To directly examine the testosterone production ratein MIS-treated animals, we isolated Leydig cells from MIS andvehicle-injected testes. Primary Leydig cells exposed to MIS had a lowertestosterone production rate and decreased expression of p450c17(hydroxylase/lyase) and luteinizing hormone (LH) receptor mRNAs than thatof vehicle-injected controls or the noninjected contralateral testis. Inconclusion, intratesticular administration of MIS caused a decline in serumtestosterone concentrations by decreasing the rate of testosteronebiosynthesis, confirming that MIS can regulate adult Leydig cell androgenproduction. The ability of MIS to down-regulate mRNA expression of thep450c17 and LH receptor genes suggests that this effect is mediatedtranscriptionally. These data indicate that, in addition to its role inembryonic differentiation of the male reproductive tract, MIS has aregulatory function in the postnatal testis. We conclude that one suchfunction is for MIS to directly inhibit adult Leydig cell steroidogenesis.