Genetics of anti-Müllerian hormone and its signaling pathway

Anti-Müllerian hormone (AMH) is a member of the TGF-β family produced essentially by the supporting somatic cells of the testis. Initially known for its inhibiting role upon the development of female internal organs, AMH has been shown to exert many other effects namely upon germ cells. Circulating AMH reflects the ovarian reserve of young developing follicles and is used to evaluate the fertility potential in assisted reproduction. The signaling pathway of AMH is both similar and different from that of other members of the TGF-β family. Like these, it signals through two distinct serine/threonine receptors, type 1 and type 2, that phosphorylate cytoplasmic effectors, the Smads. It also shares type 1 receptors and Smads with other members of the family. However, AMH is the only family member with its own, dedicated, ligand-specific type 2 receptor, AMHR2. The monogamic relationship between AMH and AMHR2 is supported by molecular studies of the Persistent Müllerian Duct Syndrome, characterized by the presence of Müllerian derivatives in otherwise normally virilized males: mutations of AMH or AMHR2 are clinically indistinguishable.