AJP - Endocrinology and Metabolism, Vol 243, Issue 2 81-E87, Copyright © 1982 by American Physiological Society
Androgen resistance syndromes
J. E. Griffin, M. Leshin and J. D. Wilson
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.
