title: Calciotrophic hormones and hyperglycemia modulate vitamin D receptor and 25 hydroxyy vitamin D 1-α hydroxylase mRNA expression in human vascular smooth muscle cells.
abstract: Estrogen receptors (ERα and ERβ), the vitamin D receptor (VDR) and 25 hydroxyy vitamin D 1-α hydroxylase (1OHase) mRNA are expressed in vascular smooth muscle cells (VSMC). In these cells estrogenic hormones modulate cell proliferation as measured by DNA synthesis (DNA). In the present study we determined whether or not the calciotrophic hormones PTH 1-34 (PTH) and less- calcemic vitamin D analog QW as well as hyperglycemia can regulate DNA synthesis and CK. E2 had a bimodal effect on VSMC DNA synthesis, such that proliferation was inhibited at 30nM but stimulated at 0.3nM. PTH at 50nM increased, whereas QW at 10nM inhibited DNA synthesis. Hyperglycemia inhibited the effects on high E2, QW and PTH on DNA only. Both QW and PTH increased ERα mRNA expression, but only PTH increased ERβ expression. Likewise, both PTH and QW stimulated VDR and 1OHase expression and activity. ERβ, VDR and 1OHase expression and activity were inhibited by hyperglycemia, but ERα expression was unaffected by hyperglycemia. In conclusion, calcitrophic hormones modify VSMC growth and concomitantly affect ER expression in these cells as well as the endogenous VSMC vitamin D system elements, including VDR and 1OHase. Some of the later changes may likely participate in growth effects. Of importance in the observation is that several regulatory effects are deranged in the presence of hyperglycemia, particularly the PTH- and vitamin D-dependent up regulation of VDR and 1OHase in these cells. The implications of these effects require further studies. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.
authors.affiliation: Institute of Endocrinology, Metabolism and Hypertension Tel- Aviv Sourasky Medical Centre and Sackler Faculty of Medicine, Tel- Aviv University, Tel- Aviv 64239, Israel. Electronic address: dsomjen10@gmail.com.
authors.forename: D
authors.initials: D
authors.lastname: Somjen
authors.affiliation: Institute of Endocrinology, Metabolism and Hypertension Tel- Aviv Sourasky Medical Centre and Sackler Faculty of Medicine, Tel- Aviv University, Tel- Aviv 64239, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Knoll
authors.affiliation: Institute of Endocrinology, Metabolism and Hypertension Tel- Aviv Sourasky Medical Centre and Sackler Faculty of Medicine, Tel- Aviv University, Tel- Aviv 64239, Israel.
authors.forename: O
authors.initials: O
authors.lastname: Sharon
authors.affiliation: Institute of Endocrinology, Metabolism and Hypertension Tel- Aviv Sourasky Medical Centre and Sackler Faculty of Medicine, Tel- Aviv University, Tel- Aviv 64239, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Many
authors.affiliation: Institute of Endocrinology, Metabolism and Hypertension Tel- Aviv Sourasky Medical Centre and Sackler Faculty of Medicine, Tel- Aviv University, Tel- Aviv 64239, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Stern
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics*; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006934:Hypercalcemia / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D014815:Vitamins / Q000494:pharmacology
chemical_list: D010281:Parathyroid Hormone; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D014815:Vitamins; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol
keywords: 1OHase; ER; ERα; Hyperglycemia; VDR; Vascular smooth muscle cells; β