Anti-Müllerian hormone in disorders of sex determination and differentiation

Abstract

Masculinisation of internal and external genitalia during foetal development depends on the existence of two discrete testicular hormones: Leydig cell-secreted testosterone drives the differentiation of the Wolffian ducts, the urogenital sinus and the external genitalia, whereas Sertoli cell-produced anti-Müllerian hormone (AMH) provokes the regression of Müllerian ducts. The absence of AMH action in early foetal life results in the formation of the Fallopian tubes, the uterus and the upper third of the vagina. In 46,XY foetuses, lack of AMH may result from testicular dysgenesis affecting both Leydig and Sertoli cell populations: in this case persistence of Müllerian remnants is associated with ambiguous or female external genitalia. Alternatively, defective AMH action may result from mutations of the genes encoding for AMH or its receptor: in this condition known as Persistent Müllerian Duct Syndrome, testosterone production is normal and external genitalia are normally virilised. Finally, AMH may be normally secreted in intersex patients with defects restricted to androgen synthesis or action, resulting in patients with female or ambiguous external genitalia with no Müllerian derivatives.