Inhibitory effect of progesterone on cell death of mouse uterine epithelium.

The protective effect of progesterone against cell death of mouse uterine epithelium was evaluated by examining the retention of 5'-[125I]iodo-2'-deoxyuridine [( 125I]IdUrd) incorporated into the whole uterus and the apoptotic index (percentage of apoptotic cells in total cells), which is a good index of physiological cell death. Castrated adult female mice were given a daily injection of oestradiol-17 beta for 3 days, and then an injection of [125I]IdUrd. They were then divided into 4 groups, which received a daily injection of vehicle only, oestradiol-17 beta (E), progesterone (P), or both oestradiol-17 beta and progesterone (EP), and were killed at intervals during these treatments for determination of 125I radioactivity retained in the whole uterus. On treatment with vehicle only, the 125I radioactivity retained in the uterus decreased rapidly, but treatment with E, P or EP reduced the loss of 125I radioactivity significantly. Progesterone did not antagonize the effect of oestradiol-17 beta on the 125I radioactivity retained in the uterus. The apoptotic index of uterine cells was examined by a similar experimental protocol, but without injection of [125I]IdUrd. In the group treated with vehicle only, the apoptotic indices of both luminal and glandular epithelia increased markedly, but the injection of E, P or EP suppressed these increases significantly. Progesterone did not antagonize the effect of oestradiol-17 beta on the apoptotic index. The apoptotic index of stroma was not affected by the injection of E, P or EP. On the other hand, progesterone completely inhibited the increase in the mitotic index of uterine epithelia induced by oestradiol-17 beta. These results show that progesterone alone or in combination with oestrogen reduced cell death in mouse uterine epithelium and that the effects of oestrogen and progesterone on uterine cell death were independent of their actions on cell division.