title: Epitestosterone: a potential new antiandrogen.
abstract: Epitestosterone (EpiT) is the 17 alpha-hydroxy epimer of testosterone (T) and a natural steroid metabolite. It has previously been shown to be a 5 alpha-reductase inhibitor. We have studied EpiT as an antiandrogen using the hamster flank organ model. One-centimeter silastic capsules of crystalline T or dihydrotestosterone (DHT) were implanted subcutaneously in female Golden Syrian hamsters to provide continuous androgenic stimulation. After 3 weeks, the pigmented spot was measured and the flank organs were fixed for histologic sectioning. The maximum surface area (SA) from a central section of the sebaceous gland and the diameter of hair follicles were measured using a computerized digitizing tablet. Following T and DHT, respectively, there was a significant increase in pigmented spot size (656/382%), sebaceous gland SA (210/315%), and mean hair follicle diameter (80/56%). A 1-cm capsule of EpiT alone had no androgenic effect. Five- and ten-fold doses of EpiT were implanted with T or DHT. Epitestosterone significantly inhibited the T-dependent stimulation of pigment, sebaceous gland, and hair follicle at either 5- and/or 10-fold excess doses. Additionally, a 10-fold dose of EpiT also inhibited DHT-dependent stimulation of all 3 cutaneous structures. We conclude that EpiT was effective as an antiandrogen and had no intrinsic androgenic activity in the hamster flank organ. It probably functions both as a competitive inhibitor of the androgen receptor and as a 5 alpha-reductase inhibitor. Pigment and sebaceous gland growth were more sensitive than the hair follicle to androgen inhibition by EpiT at the time and doses tested.
mesh_terms: D000726:Androgen Antagonists; D000818:Animals; D006224:Cricetinae; D013196:Dihydrotestosterone / Q000037:antagonists & inhibitors; D004845:Epitestosterone / Q000494:pharmacology*; D005260:Female; D006197:Hair / Q000187:drug effects; D008647:Mesocricetus; D010858:Pigmentation / Q000187:drug effects; D012627:Sebaceous Glands / Q000187:drug effects; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D000726:Androgen Antagonists; D013196:Dihydrotestosterone; D013739:Testosterone; D004845:Epitestosterone