ANTIANDROGENIC EFFECT OF RU-486 IN THE MOUSE KIDNEY

RU-486 (mifepristone) is a synthetic steroid with potent antiprogester one and antiglucocorticoid activity, that is currently used as a contr aceptive agent. In the present work we have evaluated the antiandrogen ic effect of this compound on mouse kidney, a very well known extragen ital model of androgen action by studying the effect of RU-486 on rena l parameters that depend on androgens, such as renal ornithine decarbo xylase (ODC) activity and kidney hypertrophy, as well as the inhibitor y action of mifepristone on the induction of renal ODC and kidney hype rtrophy elicited by testosterone treatment in female mice and in castr ated 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 dec reased 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 th e renal ODC induction elicited by exogenous administration of testoste rone 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 i nhibited more than 80% ODC induction produced by treatment with 5 mg/k g 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 wit h TP 100 mg/kg; (3) RU-486 was more effective in blocking the anabolic effects produced by stanozolol, a steroidal anabolizing agent, than t hose produced by testosterone; and (4) RU-486 was less effective than the nonsteroidal antiandrogen flutamide in inhibiting renal ODC activi ty in male mice. Our results clearly indicate that RU-486 possesses mo derate antiandrogenic activity in mouse kidney. The possibility that R U-486 may have similar effects in man should be considered when using this drug. (C) 1997 Elsevier Science Ltd.