Antiandrogenic effect of RU-486 in the mouse kidney.
RU-486 (mifepristone) is a synthetic steroid with potent antiprogesterone and antiglucocorticoid activity, that is currently used as a contraceptive agent. In the present work we have evaluated the antiandrogenic effect of this compound on mouse kidney, a very well known extragenital model of androgen action by studying the effect of RU-486 on renal parameters that depend on androgens, such as renal ornithine decarboxylase (ODC) activity and kidney hypertrophy, as well as the inhibitory action of mifepristone on the induction of renal ODC and kidney hypertrophy elicited by testosterone treatment in female mice and in castrated male. The results showed that: (1) 48 hr after treatment of male mice with of RU-486 (50 mg/kg, four injections) renal ODC activity decreased from 3.381 +/- 490 nmol CO2/h.g to 605 +/- 163 (SD, n = 5); (2) in female mice or orchidectomized male mice, RU-486 also inhibited the renal ODC induction elicited by exogenous administration of testosterone propionate (TP), the magnitude of the inhibition was dependent on the doses of TP and RU-486 used. While RU-486 at a dose of 25 mg/kg inhibited more than 80% ODC induction produced by treatment with 5 mg/kg TP, the same dose did not significantly affect ODC when the dose of TP was increased up to 100 mg/kg. Higher concentration of RU-486 (200 mg/kg) clearly inhibited the increase in ODC produced by treatment with TP 100 mg/kg; (3) RU-486 was more effective in blocking the anabolic effects produced by stanozolol, a steroidal anabolizing agent, than those produced by testosterone; and (4) RU-486 was less effective than the nonsteroidal antiandrogen flutamide in inhibiting renal ODC activity in male mice. Our results clearly indicate that RU-486 possesses moderate antiandrogenic activity in mouse kidney. The possibility that RU-486 may have similar effects in man should be considered when using this drug.
Tovar
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A
Department of Biochemistry, Faculty of Medicine University of Murcia, Spain.
Sánchez-Capelo
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A
Galindo
J D
JD
Cremades
A
A
Peñafiel
R
R
D000726:Androgen Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D015735:Mifepristone / Q000378:metabolism / Q000494:pharmacology*; D009919:Orchiectomy; D009955:Ornithine Decarboxylase / Q000032:analysis / Q000378:metabolism
D000726:Androgen Antagonists; D000728:Androgens; D015735:Mifepristone; D009955:Ornithine Decarboxylase