Possible role for H--Y antigen in the primary determination of sex.

Abstract

IN mammals, the genetic basis of sex determination and differentiation seems to be simple1,2. A gene or set of genes on the Y chromosome causes the indifferent embryonic gonad to develop as a testis3. Thus an ovary develops in the absence of the Y and a testis in its presence. The testis then secretes testosterone which induces male development of the accessory glands and ducts4,5. The masculinising action of testosterone on its target cells is mediated by the product of a gene on the X chromosome. This product activates all the genes required for manifestation of the male phenotype in response to circulating testosterone1. Evidence for this crucial involvement of the X chromosome in male sexual differentiation comes from a mutation of the relevant gene in the mouse (Tfm), resulting in failure to respond to testosterone. A chromosomally XY animal with this mutant gene develops testes, because the Y chromosome is present, but shows no further male differentiation, thus exhibiting the syndrome known as ‘testicular feminisation’6. This insensitivity to androgen is caused by a mutational deficiency of the nuclear–cytosol androgen-receptor protein not only in mice7–9 but also in man10. Thus the part that the X chromosome plays in male sexual differentiation has been clarified at the level of an individual gene situated on this chromosome.