Critical exposure time for androgen activation of male sexual behavior in rats.

We determined the minimum number of hours per day of testosterone (T) exposure required to activate male sexual behavior, and correlated these changes with the temporal parameters of androgen receptor occupation. For the first part of the study, castrated Long-Evans male rats received two 10 mm T-filled Silastic capsules in open flank pouches for 4, 8, 12, 16, 18, 21, or 24 hours per day over a 10 day period. Tests for male sexual behavior were conducted on days 2-3, 4-5, 7-8, and 9-10 of T treatment. A significantly higher proportion of males receiving 21 or 24 hr of daily T exposure mounted, intromitted and ejaculated compared to groups with daily T exposures of 18 hr or less. In the second part of this study we assessed whether it was necessary to maintain high levels of androgen receptor occupation during the 21-24 hr exposure period in order to activate male sexual behavior. Cell nuclear androgen receptor occupation was measured in HPAS (combined hypothalamus, preoptic area, amygdala and septum) of rats receiving 12, 21, or 24 hr of T exposure. In all three groups, nuclear androgen receptor occupation was high at the time of capsule removal, and fell significantly by 3 hr following T capsule removal. By 6 hr after T capsule removal, androgen receptor binding had fallen to castrate levels. These results demonstrate that, although relatively brief (less than or equal to 18 hr/day) exposures to testosterone can activate mounts and intromissions, significantly more responses are found in males receiving at least 21 hr of T exposure per day.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of cell nuclear androgen receptor binding and copulation in male rats by an antiandrogen, Sch 16423.

The ability of the flutamide metabolite Sch 16423 to block androgen receptor binding and inhibit masculine copulatory behavior in male rats was examined. Restoration of copulatory behavior was prevented in Sch 16423-treated rats given two 10-mm testosterone (T)-filled Silastic capsules plus 15 mg Sch 16423 daily for 11 days. Control males receiving only T-filled capsules copulated successfully. To test maintenance of copulatory behavior, T-filled capsules were implanted at the time of castration and rats received daily injections of either 0, 1, 5, 15 or 30 mg Sch 16423. Ejaculation was not prevented by Sch 16423 treatment, suggesting only a weak effect of Sch 16423 on the maintenance of copulatory behavior. An exchange assay was used to determine the effects of Sch 16423 on cell nuclear androgen receptor binding both in vivo and in vitro. For in vivo tests, castrate males bearing two 10-mm T-filled capsules received a single injection of either 0, 1, 5, or 15 mg Sch 16423 1 h prior to sacrifice. Androgen receptor binding was drastically reduced in both brain (combined hypothalamus, preoptic area, amygdala and septum) and pituitary at all doses of Sch 16423. For in vitro assays, samples from brain and pituitary were incubated with 10(-10) to 10(-6) M dihydrotestosterone (DHT), Sch 16423 or flutamide. Sch 16423 competed for androgen receptors in vitro, though not as effectively as DHT. Flutamide was a poor competitor. These results indicate that Sch 16423 effectively reduces masculine copulatory potential primarily affecting restoration of behavior, and that Sch 16423 inhibited cell nuclear androgen receptor binding both in vivo and in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)