Role of type I receptors for anti-Müllerian hormone in the SMAT-1 Sertoli cell line.
Anti-Müllerian hormone (AMH) is a member of the transforming growth factor-beta family responsible for regression of Müllerian 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.
Belville
Corinne
C
Institut National de la Santé et de la Recherche Médicale, Unité 493 sur l'Endocrinologie du Développement, Université Paris XI, 32 rue des Carnets, 92140 Clamart, France.
Jamin
Soazik P
SP
Picard
Jean-Yves
JY
Josso
Nathalie
N
di Clemente
Nathalie
N
D000818:Animals; D001483:Base Sequence; D052005:Bone Morphogenetic Protein Receptors, Type I; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D017931:DNA Primers; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D017978:Receptors, Growth Factor / Q000235:genetics* / Q000378:metabolism; D018000:Receptors, Peptide / Q000502:physiology*; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins / Q000378:metabolism; D012708:Sertoli Cells / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
D017931:DNA Primers; D034741:RNA, Small Interfering; D017978:Receptors, Growth Factor; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D014157:Transcription Factors; C084621:anti-Mullerian hormone receptor; D017346:Protein Serine-Threonine Kinases; C498214:BMPR1B protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I