Effects of Androstenedione on Pre-implantation Stages of Pregnancy in Rats

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Abstract
Administration of androstene-dione (4 or 8 mg/rat/day subcutaneously) on days 2-5 interfered with pregnancy in rats. This effect could be produced in intact, in adrenalectomized or in partially hepatectomized animals. These doses of androstenedione greatly reduced the deciduomal response of the uterus to trauma in pseudopregnant rats. Implantation was prevented, however, not because of the failure of the deciduonmal response, but because androstenedione caused expulsion of the developing eggs from the reproductive tract by Day 5 of pregnancy (i.e., before implantation). These effects appear similar to those produced by estrogens, and normal implantation occurred when progesterone was given with androstenediona. Cortisol acetate also tended to prevent the effects of androstendione on pregnancy in intact and in adrenalectomized, but not in partially hepatectomized rats. This suggests that the protective effect of cortisol is mediated by the liver. In intact or adrenalectomized immature rats, the uterus responded to administration of androstenedione with a dose-dependent increase in weight, and histological changes similar to those produced by estradiol. In ovariectomized and in ovariectomized-adrenalectomized animals, however, much smaller responses to similar doses of androstenedione were observed. In intact rats androstenedione and estradiol had an additive effect on uterine weight, but in ovariectomized-adren alectomized animals, androstenedione had no affect on the response to estradiol. These experiments show that the ovary is necessary for full expression of an estrogenic effect after administration of androstenedione. It is suggested that, in rats, androstenedione is metabolized to estrogen mainly by the ovary, and that this estrogen is then responsible for the interference with pregnancy.