Transduction pathway of anti-Müllerian hormone, a sex-specific member of the TGF-beta family.

Anti-Müllerian hormone (AMH), also called Müllerian inhibiting substance, is a member of the transforming growth factor beta (TGF-beta) family that represses the development and function of reproductive organs. Not for nothing did Professor Alfred Jost, who first discovered its existence, christen it 'hormone inhibitrice'! Anti-Müllerian hormone is thought to exert its effects through two membrane-bound serine/threonine kinase receptors, type 2 and type 1. Upon ligand binding, these drive receptor-specific cytoplasmic substrates, the Smad molecules, into the nucleus where they act as transcription factors. A type 2 receptor specific for AMH was cloned through its homology with receptors of TGF-beta family members; the identity of the type 1 receptor(s) is controversial. Three type 1 receptors for bone morphogenetic proteins (BMPs) are possible candidates, each, not surprisingly, activating BMP-specific Smad molecules, Smads 1, 5 and 8. Each receptor could be involved, depending on the cellular context. To date, AMH signaling has been explored through BMP-specific genes, because a reporter gene related to a physiological AMH function and upregulated by the hormone has not yet been tested in a cell line strongly expressing the AMH receptor(s).