RECEPTORS FOR ANTI-MULLERIAN HORMONE ON LEYDIG-CELLS ARE RESPONSIBLE FOR ITS EFFECTS ON STEROIDOGENESIS AND CELL-DIFFERENTIATION

Strong overexpression of anti-Mullerian hormone (AMH) in transgenic mi ce leads to incomplete fetal virilization and decreased serum testoste rone in the adult, Conversely, AMH-deficient mice exhibit Leydig cell hyperplasia, To probe the mechanism of action of AMH on Leydig cell st eroidogenesis, we have studied the expression of mRNA for steroidogeni c proteins in vivo and in vitro and performed a morphometric analysis of testicular tissue in mice overexpressing the hormone. We show that overexpression of AMH in male transgenic mice blocks the differentiati on of Leydig cell precursors, Expression of steroidogenic protein mRNA s, mainly cytochrome P450 17 alpha-hydroxylase/C17-20 lyase (P450c17), is decreased in transgenic mice overexpressing AMH and in AMH-treated purified Leydig cells, In contrast, transgenic mice in whom the AMH l ocus has been disrupted show increased expression of P450c17. In vitro , but not in vivo, AMH also decreases the expression of the luteinizin g hormone receptor, The effect of AMH is explained by the presence of its receptor on Leydig cells. Our results provide insight into the act ion of AMH as a negative modulator of Leydig cell differentiation and function.