Androgen-Insensitivity Syndrome as a Possible Coactivator Disease

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Abstract
Androgen-insensitivity syndromes in 46,XY fetuses result in various degrees of impairment in genital virilization.1 These syndromes are caused by mutations in the androgen receptor gene that result in decreased binding of androgen to the receptor.2-9 As a consequence, the transcriptional activity of the androgen–androgen-receptor complex is reduced, and therefore, genital virilization is reduced. The androgen receptor, like other steroid hormone receptors, has two major transactivation domains10 — activation function 1 (AF-1) in the N-terminal region11-13 and activation function 2 (AF-2) in the C-terminal ligand-binding domain14 — that interact with the target genes directly as well as indirectly by means of intermediary coactivators.15

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