Abstract:
: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)
journal_name
Neuroendocrinologyjournal_title
Neuroendocrinologyauthors
McGinnis MY,Mirth MCdoi
10.1159/000124510subject
Has Abstractpub_date
1986-01-01 00:00:00pages
63-8issue
1eissn
0028-3835issn
1423-0194journal_volume
43pub_type
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