Characterization of steroid binding specificity of the androgen receptor in human foreskin fibroblasts

Our objective was to evaluate a convenient in vitro model for measuring steroid affinities to the human androgen receptor. The ability₃ of unlabeled analogues of dihydrotestosterone (DHT) to compete with [³H]DHT for binding to the receptor in human fibroblasts was measured and expressed relative to DHT. The C-3 ketone group and the planar configuration of the A and B rings were critical for binding. Absence of the 10β-methyl group increased affinity of the androstane compounds for the receptor. The 17β-hydroxyl group was also essential for high affinity binding and addition of a 17α -methyl group enhanced binding. Binding of steroids with a Δ⁴ double bond was consistently less than that of the 5α-reduced steroids. This was true of both the androstene and estrene series. We conclude that human foreskin fibroblasts offer a useful model for in vitro studies characterizing the effects of steroid structural modifications on binding to the human androgen receptor.