17-BETA-ESTRADIOL AND SMOOTH-MUSCLE CELL-PROLIFERATION IN AORTIC-CELLS OF MALE AND FEMALE RATS

The low incidence of cardiovascular disease in women before menopause or during hormone replacement therapy suggests a protective effect of estrogens. The mechanism(s) are uncertain but may involve effects on l ipids, coagulation and the endothelium. Vascular smooth muscle cell (V SMC) proliferation also contributes to atherosclerosis. Hence, we inve stigated whether (17)beta-estradiol (E(2)) inhibits VSMC proliferation . VSMC of 6 female and 6 male Wistar Kyoto rats (WKY; age 10-12 weeks) were incubated for 23 h with E(2) and/or fetal calf serum (FCS). E(2) (10(-9)-10(-5) M) alone reduced [H-3]thymidine uptake at 10(-5) M (n= 8, p<0.05 vs. control) in female cells only. In female and male VSMC, FCS (1%) increased [H-3]thymidine uptake (4.5-fold, p<0.05 vs. control ). When given simultaneously, E(2) did not prevent this effect of FCS (1%). However, when cells were preincubated for 24 h with E(2) and the n stimulated with FCS, [H-3]thymidine uptake was reduced by E(2) at 10 (-5) M in female VSMC (n=7, p<0.05 vs FCS alone), while in male VSMC t his effect was minimal (n.s.): Both female and male VSMC expressed est rogen receptors as demonstrated by RT-PCR. Pretreatment of female VSMC cells with the E(2) receptor antagonist tamoxifen prevented the antip roliferative effects exerted by E(2). In aortic VSMC of female rats, E (2) moderately inhibited proliferation on its own and during stimulati on with FCS, while this effect was small in VSM of male rats. The expr ession of the E(2) receptor in female and male VSMC and the effects of tamoxifen suggest that this effect is mediated by E(2) receptors. (C) 1996 Academic Press, Inc.