A non-calcemic Vitamin D analog modulates both nuclear and putative membranal estrogen receptors in cultured human vascular smooth muscle cells

The Journal of Steroid Biochemistry and Molecular Biology
D SomjenN Stern

Abstract

In cultured human vascular smooth muscle cells (VSMC), estradiol-17beta (E2) induced a biphasic effect on DNA synthesis, i.e., stimulation at low concentrations and inhibition at high concentrations. Additionally, E2 increased the specific activity of creatine kinase (CK) in these cells. Observations that novel protein-bound membrane impermeant estrogenic complexes could elicit inhibition of DNA synthesis, suggested interaction via membranal binding sites. Nevertheless other effects, such as increasing CK activity were only seen with native E2 but not with E2-BSA, thus indicating that the classical nuclear receptor pathway was involved. In the present report, we confirm that human VSMC express both ERalpha and ERbeta. Further, pretreatment of cultured VSMC with the Vitamin D non-calcemic analog JK 1624 F2-2 (JKF) increased ERalpha mRNA (100-200%) but decreased ERbeta mRNA (30-40%) expression as measured by real time PCR. ERalpha protein expression assessed by Western blot analysis increased (25-50%) in parallel, whereas ERbeta protein expression declines (25-55%). Using ovalbumin bound to E2 (Ov-E2) linked to Eu (Eu-Ov-E2), to assess specific membrane binding sites, we observed that membranal binding was down regulated by JKF b...Continue Reading

Citations

Jun 16, 2015·Environment International·Ryoiti Kiyama, Yuko Wada-Kiyama
Oct 13, 2006·The Journal of Steroid Biochemistry and Molecular Biology·Dalia SomjenNaftali Stern
Dec 17, 2010·American Journal of Physiology. Renal Physiology·Luis E BeckerMarie-Luise Gross
Jul 13, 2021·Critical Reviews in Food Science and Nutrition·Saied A AboushanabElena G Kovaleva

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