268

AMH

MIF|MIS;anti-Mullerian hormone;AMH;anti-Mullerian hormone

Mullerian inhibiting factor|Mullerian inhibiting substance|anti-Muellerian hormone|muellerian-inhibiting factor|muellerian-inhibiting substance

19p13.3

protein-coding

Count: 1; Generif

Anti-Mullerian hormone (AMH) is a member of the transforming growth factor-beta family responsible for regression of Mullerian ducts during male sexual differentiation and for regulation of gonadal steroidogenesis. AMH is also a gonadal tumor suppressor which mediates its effects through a specific type II receptor and the bone morphogenetic protein (BMP)-specific Smad proteins, suggesting that AMH and BMPs could also share type I receptors, namely activin-like kinases (ALKs)2, 3 or 6. However, attempts to identify a unique AMH type I receptor among them were unsuccessful. Here, using kinase-deficient type I receptors and small interfering RNA technology, we demonstrate that, in an AMH Sertoli target cell line, ALK3 mediates AMH effects on both Smad1 activation and P450 side-chain cleavage enzyme. In addition, transfecting a combination of normal and kinase-deficient receptors, we show that ALK2 can compensate for the absence of ALK3 and probably acts in synergy with ALK3 at high concentrations of AMH to activate Smad1, whereas ALK6 has a competitive inhibitory effect. These results are a first step in understanding how AMH transduces its effects in immature Sertoli cells.