Mechanisms Regulating Male Sexual Behavior in the Rat: Role of 3α- and 3β-androstanediols1

Abstract

To assess whether naturally occurring 5α-androstanediols (5α-androstane-3α, 17β-diol and 5α-androstane-3β, 17β-diol) play a role in the regulation of male sexual behavior in the rat, their capability to restore copulatory behavior in castrated animals was evaluated. Androstanediols were chronically administered either alone or in combination with 5α-dihydrotestosterone (DHT) or with estradiol-17β (E2). Animals treated with testosterone (T), DHT, E2, and vehicle, either alone or in different combinations, served as controls. The occurrence of mounting, intromission, and ejaculation as well as detailed parameters of copulatory behavior were recorded twice per week for 3 weeks. At the end of treatments, the weights of sex accessory organs were also recorded. When 3β, 5α-androstanediol (3β-diol; 500 μg/day) was administered in combination with DHT (300 μg/day), full copulatory behavior was restored in all subjects in a manner similar to that obtained with E2 plus DHT or T plus DHT combinations, thus indicating an estrogen-like behavioral effect of 3β-diol. Administration of 3α, 5α-androstanediol (3α-diol; 500 μg/day) combined with DHT also restored sexual behavior, though to a lesser extent. When 3α-diol (500 μg/day) was simultaneously administered with E2 (5 μg/day), the copulatory behavior of castrated animals was fully restored in a fashion similar to that observed after administration of DHT plus E2 and T plus E2 combinations, indicating a potent androgen-like effect of 3α-diol. The behavioral effect of 3β-diol plus E2, was significantly less potent. When given alone, each androstanediol only partially restored copulatory behavior. Administration of 3α-diol either alone or combined with DHT or E2, induced a significant increase in ventral prostate and seminal vesicle weight, mimicking the effects of T and DHT, whereas 3β-diol had very little effect. The results suggest that androstanediols may have a role as synergizing molecules in regulating male sexual behavior in rodents. The data also provide a possible explanation for the behavioral effects of DHT when given at supraphysiological doses.