Receptors for anti-müllerian hormone on Leydig cells are responsible for its effects on steroidogenesis and cell differentiation.
Strong overexpression of anti-Müllerian hormone (AMH) in transgenic mice leads to incomplete fetal virilization and decreased serum testosterone in the adult. Conversely, AMH-deficient mice exhibit Leydig cell hyperplasia. To probe the mechanism of action of AMH on Leydig cell steroidogenesis, we have studied the expression of mRNA for steroidogenic proteins in vivo and in vitro and performed a morphometric analysis of testicular tissue in mice overexpressing the hormone. We show that overexpression of AMH in male transgenic mice blocks the differentiation of Leydig cell precursors. Expression of steroidogenic protein mRNAs, mainly cytochrome P450 17 alpha-hydroxylase/C17-20 lyase (P450c17), is decreased in transgenic mice overexpressing AMH and in AMH-treated purified Leydig cells. In contrast, transgenic mice in whom the AMH locus has been disrupted show increase expression of P450c17. In vitro, but not in vivo, AMH also decreases the expression of the luteinizing hormone receptor. The effect of AMH is explained by the presence of its receptor on Leydig cells. Our results provide insight into the action of AMH as a negative modulator of Leydig cell differentiation and function.
Racine
C
C
Institut National de la Santé et de la Recherche Médicale, Ecole Normale Supérieure, Département de Biologie, Montrouge, France.
Rey
R
R
Forest
M G
MG
Louis
F
F
Ferré
A
A
Huhtaniemi
I
I
Josso
N
N
di Clemente
N
N
D000818:Animals; D054304:Anti-Mullerian Hormone; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D018014:Gene Transfer Techniques; D006023:Glycoproteins; D006131:Growth Inhibitors / Q000502:physiology*; D007985:Leydig Cells / Q000166:cytology / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018000:Receptors, Peptide / Q000502:physiology*; D018125:Receptors, Transforming Growth Factor beta; D015398:Signal Transduction; D013256:Steroids / Q000378:metabolism*; D013735:Testicular Hormones / Q000502:physiology*
D006023:Glycoproteins; D006131:Growth Inhibitors; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; D013256:Steroids; D013735:Testicular Hormones; C084621:anti-Mullerian hormone receptor; D054304:Anti-Mullerian Hormone