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

Anti-Mullerian hormone (AMH) is a member of the TGF-beta family which elici ts its main action during male sex differentiation. This hormone is probabl y the most convenient marker of Sertoli cell differentiation and maturation throughout testicular development. Studying AMH gene regulation may thus b e one way of identifying effecters of Sertoli cell differentiation. To this end we first tried to locate and then to characterise DNA elements respons ible for in vivo transcriptional control of AMH expression. We obtained tra nsgenic mice expressing a reporter gene (LacZ), under control of various pu tative AMH regulatory sequences. Analysis of transgenic animals revealed th at activation of the AMH gene probably requires a two-step regulatory proce ss. The first step corresponds to the initial activation of the AMH gene oc curring at around 12.0 dpc. It requires the presence of regulatory DNA enco mpassed within a maximum of 370 bp upstream of the translation start site o f the gene, delimited by the presence of an upstream housekeeping gene (SAP -62). Following this initial transient phase, a second phase seems to accou nt for the persistence of AMH gene expression until the onset of puberty. A s the 370 bp regulatory region is not sufficient on its own to allow the tr iggering of this second phase, it seems possible that additional control el ements are required for normal AMH expression throughout testicular develop ment. The complete array of regulatory elements remains to be located. Mel. (C) 2001 Wiley-Liss, Inc.