Published Online
on March 28, 2005

A more recent version of this article appeared on April 5, 2005

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Submitted on September 27, 2004
Revised on January 5, 2005
Accepted on January 19, 2005

25-Hydroxyvitamin D₃-1-Hydroxylase Is Expressed in Human Vascular Smooth Muscle Cells and Is Upregulated by Parathyroid Hormone and Estrogenic Compounds

Dalia Somjen PhD, Yosef Weisman MD, Fortune Kohen PhD, Batya Gayer MSc, Rona Limor PhD, Orly Sharon BSc, Niva Jaccard MSc, Esther Knoll , and Naftali Stern MD^*

From the Institute of Endocrinology, Metabolism and Hypertension (D.S., R.L., O.S., E.K., N.S.) and the Metabolic Bone Disease Unit (Y.W., N.J.), Tel Aviv Sourasky Medical Centre and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, and Department of Biological Regulation (F.K., B.G.), Weizmann Institute of Science, Rehovot, Israel.

^* To whom correspondence should be addressed. E-mail: stern{at}tasmc.health.gov.il.

Background--1,25(OH)₂ vitamin D₃ exerts multiple effects in human vascular smooth muscle cells (VSMCs). We therefore tested the possibility that VSMCs possess an endogenous 25-hydroxyvitamin D₃-1-hydroxylase system, the final enzyme in the biosynthetic pathway of 1,25(OH)₂D₃.

Methods and Results--We assessed the expression and activity of 25-hydroxyvitamin D₃-1-hydroxylase by real-time polymerase chain reaction and the conversion of 25(OH)D₃ into 1,25(OH)₂D₃. First, 25-hydroxyvitamin D₃-1-hydroxylase mRNA was identified in cultured VSMCs by real-time polymerase chain reaction. Second, in cells treated daily (3 days) with parathyroid hormone (66 nmol/L), estradiol-17 (30 nmol/L), raloxifene (3 µmol/L), and the phytoestrogens genistein (3 µmol/L), biochainin A (3 µmol/L), and 6-carboxy biochainin A (30 nmol/L), 25-hydroxyvitamin D₃-1-hydroxylase mRNA increased by 43±13%, (P<0.05) 7±24% (P=NS), 176±28% (P<0.01), 65±11% (P<0.05), 152±24% (P<0.01), and 71±9% (P<0.05), respectively. Third, production of 1,25(OH)₂D₃ from 25(OH)D₃ was seen with a Km of 25 ng/mL and increased dose dependently after treatment with parathyroid hormone, genistein, and the phytosetrogen derivative 6-carboxy biochainin A. Estradiol-17 and biochainin A also increased the generation of 1,25(OH)₂D₃ by 40±23% (P<0.05) and 55±13% (P<0.05), respectively.

Conclusions--We provide here the first evidence for the expression of an enzymatically active 25(OH)D₃-1-hydroxylase system in human VSMCs, which can be upregulated by parathyroid hormone and estrogenic compounds. Because exogenous vitamin D inhibits VSMC proliferation, the role of this system as an autocrine mechanism to curb changes in VSMC proliferation and phenotype is a subject for future investigation.

Key words: molecular biology • vitamin D • vasculature • muscle, smooth • parathyroid hormone

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