[The synergistic abortive effect of anti-progestogen RU 38486 and aromatase inhibitors for pregnant rat].
We examined whether or not aminoglutethimide (AG) and miconazole (MCZ), as aromatase inhibitors, increase the abortive activity of RU38486 (RU) in pregnant rats. RU (2.5 mg/kg) alone or with an aromatase inhibitor (10 mg/kg) was administered orally to day 6-, 9- and 12-pregnant rats. After 24 hr, the ovaries, uterus and placental tissues were resected. Aromatase activity in the 800 x g supernatant fraction of the tissue homogenate was measured. Serum levels of progesterone (P), estradiol-17 beta (E2), prolactin (PRL) and testosterone (T) were also measured by RIA. In addition, the ovarian aromatase activity and the serum hormone levels in day 6-pregnant rats were measured 0, 3, 6, 12 and 24 hr after the oral administration on. The mean abortive rates in RU-treated day 6-, 9- and 12-pregnant rats were 75%, 62.5% and 50%, respectively. Although AG or MCZ alone did not induce abortion, they significantly increased the abortive effects of RU. The serum concentrations of P and E2 in day 6- and day 9-pregnant rats treated with RU and an aromatase inhibitor were decreased. There was no significant change in the serum concentrations of PRL and T during the experiment. Although no aromatase activity was detected in the uterus or placenta, the activity in ovarian tissue increased with the gestation period. The ovarian aromatase activity was suppressed by RU and an aromatase inhibitor, but not by RU alone. These results demonstrate that both RU and aromatase inhibitor enhance the abortion effects of RU in rats.
Sasaki
J
J
Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine.
Yamamoto
T
T
Okada
H
H
D000019:Abortifacient Agents; D000021:Abortifacient Agents, Steroidal; D000616:Aminoglutethimide / Q000494:pharmacology*; D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D004963:Estrenes / Q000494:pharmacology*; D005260:Female; D005836:Genitalia, Female / Q000201:enzymology; D008825:Miconazole / Q000494:pharmacology*; D015735:Mifepristone; D010053:Ovary / Q000201:enzymology; D011247:Pregnancy; D011372:Progestins / Q000097:blood*; D051381:Rats
D000019:Abortifacient Agents; D000021:Abortifacient Agents, Steroidal; D004963:Estrenes; D011372:Progestins; D000616:Aminoglutethimide; D015735:Mifepristone; D008825:Miconazole; D001141:Aromatase