Subcellular and molecular mechanisms regulating anti-Müllerian hormone gene expression in mammalian and nonmammalian species.

Abstract

Anti-Müllerian hormone (AMH) is best known for its role as an inhibitor of the development of female internal genitalia primordia during fetal life. In the testis, AMH is highly expressed by Sertoli cells of the testis from early fetal life to puberty, when it is downregulated by the action of testosterone, acting through the androgen receptor, and meiotic spermatocytes, probably acting through TNFalpha. Basal expression of AMH is induced by SOX9; GATA4, SF1, and WT1 enhance SOX9-activated expression. When the hypothalamic-pituitary axis is active and the negative effect of androgens and germ cells is absent, for example, in the fetal and neonatal periods or in disorders like androgen insensitivity, FSH upregulates AMH expression through a nonclassical cAMP-PKA pathway involving transcription factors AP2 and NFkappaB. The maintenance and hormonal regulation of AMH expression in late fetal and postnatal life requires distal AMH promoter sequences. In the ovary, granulosa cells express AMH from late fetal life at low levels; DAX1 and FOG2 seem to be responsible for negatively modulating AMH expression. Particular features are observed in AMH expression in nonmammalian species. In birds, AMH is expressed both in the male and female fetal gonads, and, like in reptiles, its expression is not preceded by that of SOX9.