title: Antagonism of the estradiol-mediated repression of microsomal 3 beta-hydroxysteroid dehydrogenase activity in rat liver by antiestrogenic substances.
abstract: 5 alpha-Dihydrotestosterone, 17-hydroxyprogesterone caproate, 2-methoxyestrone and a number of nonsteroidal antiestrogens (clomiphene citrate, nafoxidine hydrochloride, tamoxifen, MER-25) were tested for their ability to block estradiol-mediated repression of the androgen-dependent 3 beta-hydroxysteroid dehydrogenase activity of male rat liver. With the exception of 5 alpha-dihydrotestosterone, which induced activity in females, none of these substances affected 3 beta-hydroxysteroid dehydrogenase activity when administered alone to otherwise untreated male and female rats. Tamoxifen (100 or 500 micrograms/day) was the only substance which prevented a decrease in enzyme activity when given simultaneously with estradiol (5 micrograms/day). The estradiol-mediated decrease in activity was not antagonized by a 100-fold higher dose of androgen (5 alpha-dihydrotestosterone, 0.5 mg/day), demonstrating the potent antiandrogenic effect of estradiol on this hepatic androgen-dependent enzyme activity.
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000728:Androgens / Q000502:physiology; D000818:Animals; D004958:Estradiol / Q000502:physiology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D012727:Sex Characteristics
chemical_list: D000728:Androgens; D004965:Estrogen Antagonists; D004958:Estradiol; D015096:3-Hydroxysteroid Dehydrogenases