Androgen resistance syndromes

Hereditary defects that impede androgen action cause resistance to the hormone both during embryogenesis and in later life and hence usually cause developmental defects of the male urogenital tract. In genetic males such defects produce a phenotypic spectrum ranging from infertile but otherwise normal men to individuals with varying degrees of ambiguous genitalia to phenotypic women. These disorders can be classified on the basis of the step in androgen action that is impeded by the individual mutations. 5 alpha-Reductase deficiency is an autosomal recessive enzyme defect that impairs the conversion of testosterone to dihydrotestosterone. The internal male genital tract virilizes normally, but the external genitalia are predominantly female in character. The syndrome is the result of one of several mutations that impair the function of the 5 alpha-reductase enzyme. A variety of disorders influence the androgen receptor that mediates the action of both testosterone and dihydrotestosterone. At least four phenotypic variants can be distinguished: complete testicular feminization, incomplete testicular feminization, the Reifenstein syndrome, and the infertile male syndrome, each of which is inherited as an X-linked trait. Absence of receptor binding is found commonly in complete testicular feminization, but qualitative and/or less severe quantitative defects in receptor function can be associated with all four variants. A third type of disorder, receptor positive resistance, also causes variable defects in male development and is associated with normal 5 alpha-reductase activity and normal androgen receptor. The underlying defect is presumed to lie at the intranuclear site or sites of action of the hormone-receptor complex.