PHYSIOLOGY AND PATHOPHYSIOLOGY OF ANDROGEN ACTION

Knowledge of the physiology of male sexual differentiation and the cli nical presentation of androgen insensitivity syndromes (AIS) has red t o an increasing understanding of the mechanisms of androgen action. An drogens induce their specific response via the androgen receptor (AR), which in turn regulates the transcription of androgen-responsive targ et genes. The androgen-dependent development of male genital structure s and the induction of the normal male phenotype depends on the presen ce of an intact AR. Structural alterations leading to malfunction of t he AR are associated with variable inhibition of virilization despite normal or even supranormal serum levers of androgens. The mapping, clo ning and sequencing of the AR gene have facilitated new insights into the study of androgen action. Functional investigation of the normal a nd the mutant AR in vivo as well as in vitro has led to the characteri zation of the distinct molecular steps involved in the normal androgen action pathways that are inhibited in the androgen insensitivity synd rome.