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 lipids, coagulation and the endothelium. Vascular smooth muscle cell (VSMC) proliferation also contributes to atherosclerosis. Hence, we investigated whether 17 beta-estradiol (E2) inhibits VSMC proliferation. VSMC of 6 female and 6 male Wistar Kyoto rats (WKY; age 10-12 weeks) were incubated for 24 h with E2 and/or fetal calf serum (FCS). E2 (10(-9)-10(-5) M) alone reduced [3H]thymidine uptake at 10(-5) (n=8, p<0.05 vs control) in female cells only. In female and male VSMC, FCS (1%) increased [3H]thymidine uptake (4.5-fold, p<0.05 vs. control). When given simultaneously, E2 did not prevent this effect of FCS (1%). However, when cells were preincubated for 24 h with E2 and then stimulated with FCS, [3H]thymidine uptake was reduced by E2 at 10(-5) M in female VSMC (n=7, p<0.05 vs FCS alone), while in male VSMC this effect was minimal (n.s.): Both female and male VSMC expressed estrogen receptors as demonstrated by RT-PCR. Pretreatment of female VSMC cells with the E2 receptor antagonist tamoxifen prevented the antiproliferative effects exerted by E2. In aortic VSMC of female rats, E2 moderately inhibited proliferation on its own and during stimulation with FCS, while this effect was small in VSM of male rats. The expression of the E2 receptor in female and male VSMC and the effects of tamoxifen suggest that this effect is mediated by E2 receptors.
Espinosa
E
E
Cardiovascular Research, University Hospital, Bern, Switzerland.
Oemar
B S
BS
Lüscher
T F
TF
D000818:Animals; D001011:Aorta / Q000166:cytology* / Q000187:drug effects; D001483:Base Sequence; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D017931:DNA Primers; D004958:Estradiol / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D011960:Receptors, Estrogen / Q000187:drug effects / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D011960:Receptors, Estrogen; D013629:Tamoxifen; D004958:Estradiol