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Jun Kawagoe, Masahide Ohmichi, Seiji Tsutsumi, Tsuyoshi Ohta, Kazuhiro Takahashi, Hirohisa Kurachi, Mechanism of the Divergent Effects of Estrogen on the Cell Proliferation of Human Umbilical Endothelial Versus Aortic Smooth Muscle Cells, Endocrinology, Volume 148, Issue 12, 1 December 2007, Pages 6092–6099, https://doi.org/10.1210/en.2007-0188
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Diverse estrogen actions are controlled via estrogen receptors (ERs). Mechanisms of action of ERs are modulated by various factors such as ER subtypes, conformation of the ER-ligand complex, and recruitment of coregulator complexes to a target gene promoter. Estrogen exerts divergent actions on vascular cells; namely it increases endothelial cell and inhibits smooth muscle cell growth, resulting in a vasoprotective action. We particularly focused on these divergent effects and examined the mechanisms. The effects of raloxifene, which shows estrogen-like vasoprotective actions, were also examined. To examine the effects of 17β-estradiol (E2) and raloxifene on human aortic smooth muscle cells (HASMCs) and human umbilical venous endothelial cells (HUVECs), we evaluated the effect of E2 and raloxifene on transcriptional activity, recruitment of the coregulator complex to a target gene promoter, and acetylation of histone of both the IGF-I and COX-2 genes. Treatment with E2 or raloxifene increased both IGF-I and cyclooxygenase (COX)-2 mRNA expression in HUVECs, whereas they attenuated the serum-induced increase of these genes in HASMCs. Treatment by E2 and raloxifene induced recruitment of coactivator complex and histone acetylation at both the IGF-I and COX-2 gene promoter in HUVECs. In contrast, in HASMCs, E2, and raloxifene attenuated the serum-induced recruitment of coactivator complexes and histone acetylation at both the IGF-I and COX-2 gene promoters. Estrogen and raloxifene exert divergent transcriptional regulation on both mRNA expression and the remodeling of IGF-I and COX-2 gene promoters in HUVECs vs. HASMCs.
