[The effect of RU486 and progesterone on luteal function during pregnancy]

In order to investigate the role of progesterone in the maintenance of pregnancy, an anti-progesterone agent, RU486 (RU) was injected subcutaneously into pregnant rats on day 12 (D12), and morphological changes of the uterus as well as endocrinological changes were observed. In all rats injected with RU, abortion occurred with macroscopic and microscopic intrauterine hemorrhage and degeneration or delivery of conceptuses. Endocrinologically, the levels of progesterone decreased rapidly 48 hours after the injection, while the levels of estradiol showed a tendency to increase. As progesterone is mainly produced by the corpus luteum but not by the placenta in rats, the decrease in progesterone is suspected to be due to luteolysis. Then in order to clarify the mechanism of luteolysis induced by RU and the effects of progesterone on this phenomenon, the dynamics of the luteotrophic factors (estradiol, LH, PRL) and specific binding capacity of the ovaries to LH/hCG were investigated in D7 pregnant rats treated with RU 1 mg/kg alone (RU group) or with both RU 1 mg/kg and progesterone 50mg/kg (RU + P group). The serum levels of progesterone in the RU group decreased significantly after 72 hours of administration, while those in the RU + P group remained within the levels of the control group. However, serum levels of luteotrophic factors in the RU group did not decrease, and some of them were even higher than those in the control group. In the RU + P group, luteotrophic factors remained within control levels. On the other hand, the specific bindings of LH/hCG to ovarian homogenates decreased significantly after 72 hours in the RU group. But in the RU + P group, the specific bindings were kept at the same levels as the controls. Scatchard analysis of these results disclosed that in the RU group, both affinity and numbers of receptors decreased compared to the controls, and that in the RU + P group only affinity decreased transiently and afterwards recovered quickly. From these results, it is concluded that deterioration of affinity and numbers of ovarian LH/hCG receptors seems to be one of the factors which induce luteolysis in pregnant rats treated with RU, and that progesterone can spare the effect of RU on the corpus luteum during pregnancy.