[Androgen insensitivity syndromes]

Abstract

The syndromes of androgen resistance illustrate a special field of endocrinology, that is pathology of target-tissues. These syndromes are responsible for male pseudohermaphroditism and provoke in XY subjects, with a normal testicular androgen secretion, abnormalities in the phenotype with all the possibilities from an "idealistically" female phenotype in the testicular feminization syndrome to an almost normal male phenotype in the mildest forms of the incomplete syndrome. Understanding of these syndromes has strongly benefited of progress in biochemistry and molecular biology concerning the mechanism of action of androgens. On the other hand, understanding androgen mechanism expanded markedly from parallel clinical observation and biochemical investigation permitted by methodological progress: plasma hormones assays, 5 alpha-reductase and androgen receptor qualitative and quantitative determinations. The complete form of the testicular feminization syndrome seems to be due--in most cases--to an absence of the androgen receptor whereas the incomplete forms of the syndrome are related either to insufficient amount or qualitative alteration of the receptor or to a defect of 5 alpha-reductase, the key-enzyme which transforms testosterone to its active metabolite dihydrotestosterone in androgen target-cells. In some cases (approximately equal to 10%) the mechanism of androgen insensitivity could not be identified. The abnormality might be downstream the receptor at various possible steps = binding of the complex androgen-receptor to the chromatin, transcription or post-transcription process. These cases can be useful models for understanding the ultimate steps of the androgen mechanism of action.