Disorders of Sex Development in Males: Molecular Genetics, Epigenetics, Gender Identity, and Cognition

Abstract

Male sex development is a complex process of events involving genetic, epigenetic, and hormonal factors with androgens playing a major role. The formation of testes in 46,XY individuals establishes the male gonadal sex. Hormones produced by the testes, especially testosterone and anti-Mullerian hormone, play essential roles in male sex differentiation; conversely, defects in the production and action of these hormones result in disorders of sex development (DSD). In this chapter, the genetic, epigenetic, and hormonal factors controlling male sex determination and differentiation are reviewed. By discussing subjects with defects in androgen production and action, particularly those with 17beta-hydroxysteroid dehydrogenase-3 deficiency, 5alpha-reductase-2 deficiency, and androgen insensitivity syndrome, the roles of androgens in male sex differentiation, gender identity, and cognitive function are emphasized. The issue of the complex interaction of nature versus nurture is addressed.