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25 hydroxy-vitamin D3-1α hydroxylase expression and activity in cultured human osteoblasts and their modulation by parathyroid hormone, estrogenic compounds and dihydrotestosterone

2007; Elsevier BV; Volume: 107; Issue: 3-5 Linguagem: Inglês

10.1016/j.jsbmb.2007.03.048

1879-1220

Dalia Sömjen, Sara Katzburg, Naftali Stern, Förtüne Kohen, Orly Sharon, Rona Limor, Niva Jaccard, David Hendel, Yosef Weisman,

Bone health and osteoporosis research

Human osteoblasts (hOB) produce and respond to 1,25(OH)2D3 (1,25D), suggesting an autocrine/paracrine system. We therefore examined hormonal modulation of the expression and activity of 25 hydroxy-vitamin D3-1α hydroxylase (1-Ohase) in hOB. Cells from pre- and post-menopausal women or men, were treated with estrogenic compounds and 1-OHase expression and activity were measured. 1-OHase mRNA expression was highest in pre-menopausal women hOB and was increased by all hormones tested. In post-menopausal hOB all hormones except biochainin A (BA) and genistein (G) increased 1-OHase mRNA expressions to less extent. In male-derived hOB only dihydrotestosterone (DHT) and carboxy BA (cBA) increased 1-OHase mRNA expression. 1,25D production from 25(OH)D3 had a Km of ∼769–400 ng/ml (1.92–1.07 μM) and Vmax of 31.3–17.4 ng/ml (0.078–0.044 μM/60 min/5 × 106 cells) respectively, and was increased by all hormones except raloxifene (Ral) with higher stimulation in pre- than in post-menopausal cells. Only BA was almost five times more potent in pre- rather than post-menopausal hOBs. In male hOB only DHT and cBA increased 1,25D production whereas estradiol-17β (E2) had no effect and BA decreased it. These results provide evidence for the expression of 1-OHase mRNA and production of 1,25D in hOBs, which are age and sex dependent and are hormonally modulated. The role of this local autocrine/paracrine 1,25D system in bone physiology deserves further investigation.