Hormones in male sexual development

A fascinating aspect of development is the potential of sexually undifferentiated embryos to generate male or female individuals. Our knowledge of mammalian sex determination and differentiation has increased steadily in recent years. After presenting a brief overview of gonadal development and sexual determination, this article reviews recent findings concerning male sexual differentiation. In particular, we focus on the three essential hormones secreted by the testes—androgens, MIS, and Insl3—all of which cause male-specific development of the bipotential reproductive system.

In mammals, genetic sex is determined by inheritance of either an X or Y chromosome from the male gamete. The initial stages of gonadal and genital development of male and female embryos are indistinguishable by morphological criteria. In females, Müllerian ducts give rise to uterus, fallopian tubes, and proximal vagina, while in males, Wolffian ducts develop into multiple reproductive organs including vas deferens, seminal vesicles, and epididymis. The classic experiment of Jost (Jost 1947; Jost 1953) demonstrated that female differentiation occurs irrespective of the genetic sex in the absence of testicular hormones. Current studies indicate that male differentiation requires the secretion of three testicular hormones. Müllerian-inhibiting substance (MIS), also named Müllerian-inhibiting factor (MIF) or anti-Müllerian hormone (AMH), produced by fetal Sertoli cells induces regression of the Müllerian ducts. Testosterone, produced by Leydig cells, promotes development of Wolffian duct derivatives and masculinization of the external male genitalia. Finally, insulin-like 3 (Insl3) mediates transabdominal testicular descent into the scrotum (Nef and Parada 1999; Zimmermann et al. 1999). In females, differentiation occurs when the absence of MIS allows development of the Müllerian structures, the lack of androgens permits degeneration of Wolffian ducts, and the absence of Insl3 maintains the gonads in the abdomen.