STEROIDOGENIC FACTOR-I REGULATES TRANSCRIPTION OF THE HUMAN ANTI-MULLERIAN HORMONE-RECEPTOR

Anti-mullerian hormone type II receptor (AMHRII) is a serine/threonine receptor and a member of type II receptors of the transforming growth factor beta superfamily, AMHRII has been recently identified in human s, mice, rats, and rabbits. In the male embryo, the AMHRII gene has be en shown to be expressed in Sertoli's cells, in Leydig's cells and in the mesenchymal cells surrounding the mullerian duct. To determine the functional region of the AMHRII promoter as well as the factors contr olling AMHRII gene expression, we used a 1.1-kilobase DNA fragment fro m the 5'-flanking region of the human AMHRII gene to generate a series of deletion or mutation and analyzed the resulting transcriptional ac tivities after transfection of the NT2/D1 teratocarcinoma cell line, O ur results indicate that maximal expression of the AMHRII promoter in this particular cell line, a cell line positive for endogenous AMHRII expression, requires a conserved estrogen receptor half-site element ( AGGTCA) identical to the binding element for steroidogenic factor-1 (S F-1). Studies of this SF-1 binding element using gel mobility shift, a ntibody supershift assays, and transient transfections of reporter con structs indicate that SF-1 can bind and transactivate the AMHRII promo ter. Finally, SF-1 protein expression in human male embryos was shown to display a good coincidence with the previously reported AMHRII expr ession profile. We then propose that SF-1 may be a key transcriptional regulator of AMHRII gene expression during early human development.