CLONING, EXPRESSION, AND ALTERNATIVE SPLICING OF THE RECEPTOR FOR ANTI-MULLERIAN HORMONE

Anti-Mullerian hormone, also called Mullerian-inhibiting substance or factor, is a glycoprotein dimer belonging to the transforming growth factor-beta superfamily and synthesized by immature Sertoli cells and postnatal granulosa cells. Anti-Mullerian hormone plays a key role in sex differentiation by inducing the regression of Mullerian ducts in the male fetus. It is also responsible for the stunting and masculinization of fetal ovaries in bovine freemartin fetuses and may be involved in the control of follicular maturation in the postnatal ovary. Using a degenerate probe for a consensus region of the transforming growth factor-beta receptor superfamily to screen a complementary DNA library from rabbit fetal ovaries, we cloned a complementary DNA coding for a transmembrane serine/threonine kinase, which is expressed around the fetal Mullerian duct, in fetal and adult granulosa cells, and in immature Sertoli cells. Two transcripts, generated by alternative splicing of an exon coding for an N-terminal 61-amino acid domain, are strongly expressed in anti-Mullerian hormone target organs and Sertoli cells. The longer, 569-amino acid, isoform binds anti-Mullerian hormone when transiently expressed in COS cells and is believed to encode its functional receptor.