Estrogen mediates the protective effects of pregnancy and chorionic gonadotropin in a mouse model of vascular injury

To determine why pregnancy protects against intimal proliferation in a mous e model of vessel injury, we administered chorionic gonadotropin to intact and ovariectomized female mice. Chorionic gonadotropin markedly suppressed intimal proliferation in intact but not in ovariectomized female mice, indi cating that the protective effects of chorionic gonadotropin require ovaria n function. To test whether estrogen or progesterone might mediate the prot ective effects of pregnancy and chorionic gonadotropin, we administered est rogen and progesterone to ovariectomized mice. Estrogen administration to o variectomized mice to achieve the elevated levels seen in pregnancy was suf ficient to reproduce the marked suppression of intimal proliferation in res ponse to vessel injury. Progesterone administration reduced intimal prolife ration to a lesser degree and was correlated with increases in estrogen to levels seen in nonpregnant female mice. Staining for proliferating cell nuc lear antigen suggested that estrogen reduced medial and intimal cell prolif eration. Both the classic estrogen receptor-alpha and the recently discover ed estrogen receptor-beta are present in vascular tissue as assessed by imm unohistochemistry, providing a possible mechanism for the effects of estrog en. These results suggest that the protective effects of estrogen do not pl ateau at levels seen in normal females but increase further with estrogen l evels up through levels seen during pregnancy.