Oral contraceptive steroids and atherosclerosis: lipogenesis in human arterial smooth muscle cells and dermal fibroblasts in presence of lipoprotein-deficient serum from oral contraceptive users.
The incorporation of [14C]-acetate into lipids by cultured human arterial smooth muscle cells and dermal fibroblasts was studied in the presence of lipoprotein-deficient serum from oral contraceptive users (OC) and control women. Exposure to OC serum: 1) significantly increased the synthesis of cholesterol above controls in both fibroblasts (+25-56%) and smooth muscle cells (+28-42%) without a significant change in the synthesis of lecithin; and 2) resulted in increased cholesterol/lecithin ratios in newly synthesized lipids which were higher than controls in both fibroblasts (+50%) and smooth muscle cells (+30%). In vitro addition of the steroid ingredients of the "pill" to the growth medium containing control serum did not result in a stimulation of lipogenesis by the cells. [3H] - mevalonate incorporation into cholesterol was no different with OC and control serum, indicating that the stimulation noted in cholesterol synthesis by OC serum was due to an increased HMG-CoA reductase activity. These findings suggest that increased sterol synthesis in arterial smooth muscle cells of oral contraceptive users may be one pathogenetic factor which adversely influences their risk of atherosclerosis.
D000328:Adult; D001158:Arteries / Q000378:metabolism*; D001161:Arteriosclerosis / Q000139:chemically induced*; D002784:Cholesterol / Q000096:biosynthesis; D003276:Contraceptives, Oral / Q000009:adverse effects*; D003280:Contraceptives, Oral, Synthetic / Q000009:adverse effects*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000172:deficiency*; D008656:Mestranol / Q000009:adverse effects; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009640:Norethindrone / Q000009:adverse effects; D012867:Skin / Q000378:metabolism
D003276:Contraceptives, Oral; D003280:Contraceptives, Oral, Synthetic; D008074:Lipoproteins; D002784:Cholesterol; D008656:Mestranol; D009640:Norethindrone