GATA-1 is a potential repressor of anti-Mullerian hormone expression during the establishment of puberty in the mouse

Anti-Mullerian hormone (AMH), also known as Mullerian inhibiting substance (MIS), is one of the earliest and best-known markers of Sertoli cell differ entiation and is expressed until around puberty. The present study is aimed at the better understanding of the molecular pathways involved in testicul ar development and establishment of adult functions with regards to AMH reg ulation. We found, within the mouse AMH promoter, putative GATA motifs (A/T )GATA(A/G), known to be specifically bound by members of the GATA transcrip tion factor family. We then carried out RNase protection assays and immunoh istochemical techniques aimed at comparing precisely the chronological expr ession patterns of AMH and GATA-1, this latter being expressed in the testi s after birth. Using both approaches we found an inverse and close relation ship between AMH and GATA-1 mRNA and protein expression during the pre-pube rtal period. These results allowed us to define a transitory 4-5-day period , starting from 3 dpp when both proteins are heterogeneously expressed in S ertoli cells and showed that the appearance of GATA-1 is associated with th e decrease of AMH expression in these cells. Furthermore DNA-protein intera ction in in vitro studies showed first that GATA-1 binds with various affin ities on sites found in the AMH promoter and second that the proximity of t he two strongest affinity sites leads to a synergistic binding effect. Alto gether, the present study suggests that GATA-1 participates in AMH gene rep ression during the pre-pubertal period. Mel. Reprod. Dev. 56:124-138, 2000. (C) 2000 Wiley-Liss, Inc.