Receptors for anti-Müllerian hormone on Leydig cells are responsible for its effects on steroidogenesis and cell differentiation

Receptors for anti-Müllerian hormone on Leydig cells are responsible for its effects on steroidogenesis and cell differentiation

^*Unité de Recherches sur l’Endocrinologie du Développement, Institut National de la Santé et de la Recherche Médicale, Ecole Normale Supérieure, Département de Biologie, 92120 Montrouge, France; ^†Unité de Recherches sur la Pathologie Hormonale Moléculaire, Institut National de la Santé et de la Recherche Médicale, Hôpital Debrousse, 69322 Lyon, France; and ^‡Department of Physiology, University of Turku, 20520 Turku, Finland

Communicated by Maria Iandolo New, New York Hospital–Cornell Medical Center, New York, NY (received for review July 22, 1997)

Abstract

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 17α-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 increased 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.

Footnotes

↵ § To whom reprint requests should be addressed at: Institut National de la Santé et de la Recherche Médicale 293, 1 rue Maurice Arnoux, 92120 Montrouge, France. e-mail: clemente{at}wotan.ens.fr.
ABBREVIATIONS:

AMH,

anti-Müllerian hormone;

AMHR,

AMH receptor;

hAMH,

human AMH;

MT,

metallothionein 1;

RT-PCR,

reverse transcriptase–PCR;

FSH,

follicle-stimulating hormone;

DHT,

dihydrotestosterone;

LH,

luteinizing hormone;

LHR,

LH receptor;

StAR,

steroidogenic acute regulatory protein;

HSD,

hydroxysteroid dehydrogenase