Action of oestrogens and antioestrogens on oestrogen-inducible cytoplasmic and androgen-inducible microsomal activity of 3 alpha-hydroxysteroid dehydrogenase in male rat kidney.
The influence of steroidal and non-steroidal antioestrogenic compounds on the effect of systemically administered oestradiol (OE2) and diethylstilboestrol (DES) was investigated in adult male rats with intact gonads. In this animal model, oestrogens induced the NADP-dependent cytoplasmic activity and prevented the inductive action of androgens on NADP-dependent microsomal activity of renal 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSDH). Simultaneous administration of tamoxifen (0.5 mg/day) with OE2 (5 microgram/day) or DES (10 microgram/day) for 10 days completely blocked the inductive effect of OE2 on cytoplasmic 3 alpha-HSDH, whereas, in the case of the microsomal enzyme, the repressive effects of OE2 and DES were antagonized only to 28 and 16% respectively. Simultaneous administration of 5 alpha-dihydrotestosterone (DHT; 0.5 mg/day) for 10 days antagonized the inductive effect of OE2 on the cytoplasmic enzyme activity to 86% and completely by-passed the repressive effects of OE2 and DES on the microsomal enzyme activity. It is concluded that oestrogenic induction of renal cytoplasmic 3 alpha-HSDH involves an oestrogen receptor mechanism which, in this animal model, can be antagonized by tamoxifen. In contrast, oestrogenic repression of renal microsomal 3 alpha-HSDH is obviously the consequence of the strong antigonadotrophic activity of oestrogens leading to subsequent repression of testicular androgen secretion by mechanisms which can be only weakly antagonized by tamoxifen. Exogenous DHT, even in the presence of OE2 or DES, completely compensates for this centrally mediated deficit of peripheral androgen.
D015096:3-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis*; D000818:Animals; D004054:Diethylstilbestrol / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D013629:Tamoxifen / Q000494:pharmacology
D004965:Estrogen Antagonists; D013196:Dihydrotestosterone; D013629:Tamoxifen; D004958:Estradiol; D004054:Diethylstilbestrol; D015096:3-Hydroxysteroid Dehydrogenases