DUAL REGULATION OF LUTEAL PROGESTERONE PRODUCTION BY ANDROSTENEDIONE DURING SPONTANEOUS AND RU486-INDUCED LUTEOLYSIS IN PREGNANT RATS

The effect of androstenedione on luteal progesterone production was st udied during luteolysis preceding parturition as well as that induced by the antiprogestin RU486 in late pregnant rats. Luteal cells from an imals on days 19, 20 or 21 of pregnancy and incubated with 10 mu M and rostenedione increased progesterone production by 99, 136, and 277%, r espectively. The animals receiving androstenedione (10 mg/rat s.c.) on day 19 of pregnancy showed an increase in serum progesterone levels, a decline in luteal 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) a ctivity and an increase in corpus luteum weight without modifying 20 a lpha-hydroxysteroid dehydrogenase (20 alpha-HSD) activity on day 21 of pregnancy. Androstenedione and testosterone but not dihydrotestostero ne were able to prevent the decrease in serum progesterone concentrati on and corpus luteum weight observed 58 h after treatment with RU486 ( 2 mg/kg) on day 18 of pregnancy. However, the three androgens studied inhibited the luteal 3 beta-HSD activity but 20 alpha-HSD activity was not affected, when compared with animals receiving RU486 alone. The c o-administration of androstenedione with the aromatase inhibitor 4-hyd roxyandrostenedione or with the specific antioestrogen ICI 164,384 did not modify the effects induced by androstenedione in RU486-treated ra ts, indicating that the action of androstenedione on progesterone prod uction and secretion at the time of luteolysis seems to occur through an androgenic mechanism and is not mediated by previous conversion of the androgens to oestrogens, In all experiments the high luteal 20 alp ha-HSD activity, that characterizes a luteolytic process, was not modi fied by androgens. Androstenedione administered to adrenalectomized ra ts was also able to prevent the decrease in serum progesterone concent ration observed in spontaneous or RU486-induced luteolysis. The admini stration of androstenedione to RU486-treated rats induced a decrease i n luteal progesterone content concomitant with an increase in serum pr ogesterone levels. These studies demonstrate that androgens during lut eolysis, are able to stimulate luteal progesterone secretion, prevent the loss in corpora lutea weight and enhance the decrease in 3 beta-HS D activity, without affecting the increase in 20 alpha-HSD activity.