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 ability 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 10 beta-methyl group increased affinity of the androstane compounds for the receptor. The 17 beta-hydroxyl group was also essential for high affinity binding and addition of a 17 alpha-methyl group enhanced binding. Binding of steroids with a delta 4 double bond was consistently less than that of the 5 alpha-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.
D001667:Binding, Competitive; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000031:analogs & derivatives / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008297:Male; D011944:Receptors, Androgen / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*
D011944:Receptors, Androgen; D011987:Receptors, Steroid; D013196:Dihydrotestosterone