Anti-Müllerian hormone is a gonadal cytokine with two circulating forms and cryptic actions

Abstract

Anti-Müllerian hormone (AMH) is a multi-faceted gonadal cytokine. It is present in all vertebrates with its original function in phylogeny being as a regulator of germ cells in both sexes, and as a prime inducer of the male phenotype. Its ancient functions appear to be broadly conserved in mammals, but with this being obscured by its overt role in triggering the regression of the Müllerian ducts in male embryos. Sertoli and ovarian follicular cells primarily release AMH as a prohormone (proAMH), which forms a stable complex (AMHN,C) after cleavage by subtilisin/kexin-type proprotein convertases or serine proteinases. Circulating AMH is a mixture of proAMH and AMHN,C, suggesting that proAMH is activated within the gonads and putatively by its endocrine target-cells. The gonadal expression of the cleavage enzymes is subject to complex regulation, and the preliminary data suggest that this influences the relative proportions of proAMH and AMHN,Cin the circulation. AMH shares an intracellular pathway with the bone morphogenetic protein (BMP) and growth differentiation factor (GDF) ligands. AMH is male specific during the initial stage of development, and theoretically should produce male biases throughout the body by adding a male-specific amplification of BMP/GDF signalling. Consistent with this, some of the male biases in neuron number and the non-sexual behaviours of mice are dependent on AMH. After puberty, circulating levels of AMH are similar in men and women. Putatively, the function of AMH in adulthood maybe to add a gonadal influence to BMP/GDF-regulated homeostasis.