In vivo analysis of the regulation of the anti-Mullerian hormone, as a marker of Sertoli cell differentiation during testicular development, reveals a multi-step process

Anti-Müllerian hormone (AMH) is a member of the TGF-β family which elicits its main action during male sex differentiation. This hormone is probably the most convenient marker of Sertoli cell differentiation and maturation throughout testicular development. Studying AMH gene regulation may thus be one way of identifying effectors of Sertoli cell differentiation. To this end we first tried to locate and then to characterise DNA elements responsible for in vivo transcriptional control of AMH expression. We obtained transgenic mice expressing a reporter gene (LacZ), under control of various putative AMH regulatory sequences. Analysis of transgenic animals revealed that activation of the AMH gene probably requires a two-step regulatory process. The first step corresponds to the initial activation of the AMH gene occurring at around 12.0-dpc. It requires the presence of regulatory DNA encompassed within a maximum of 370-bp upstream of the translation start site of the gene, delimited by the presence of an upstream housekeeping gene (SAP-62). Following this initial transient phase, a second phase seems to account for the persistence of AMH gene expression until the onset of puberty. As the 370-bp regulatory region is not sufficient on its own to allow the triggering of this second phase, it seems possible that additional control elements are required for normal AMH expression throughout testicular development. The complete array of regulatory elements remains to be located.