Endocrine Abstracts

Vitamin D receptors (VDRs) are expressed in bone and vascular cells which also respond to vitamin D treatment by modulation of cell proliferation measured by DNA synthesis and energy metabolism measured by CK specific activity. We have previously observed that vitamin D-related compounds target several genes which affect cell proliferation, including mRNA expression of estrogen receptor (ER)α, ERβ, VDR, 1α hydroxylase of 25OHD3 (1OHase) and 12 and 15 lipoxygenases (LOs) measured by real-time PCR. In the present study we compared our newly synthesized analog, 1α,25-dihydroxy-9-methylene-19-norvitamin D3 (JK152 (JK)) on bone and vascular cells to other non-calcemic vitamin D analogs. Human bone cell line SaSO₂, dose-dependently responded to JK by increased DNA synthesis and stimulated CK specific activity similar to CB 1093 (CB) and EB 1089 (EB) (50–80 and 40-80% respectively compared to 60–80% by JK). JK also inhibited DNA synthesis in primary human vascular smooth cells (VSMC) dose-dependently similarly to CB and EB (80–50% compared to 75–60% by CB). VSMC expressed 12LO, 15LO, ERα, ERβ, VDR, and 1OHase mRNA. Daily treatment for 3 days with JK, CB and EB stimulated 12LO and 15LO mRNA expression (35% by JK, 0% by CB and 250% by EB of 12LO and 35% by JK, 230% by CB and 35% by EB of 15LO). JK stimulated ERα (150% by JK, 220% by CB and 190% by EB) with no effect on ERβ. Finally, JK stimulated VDR (200% by JK, 220% by CB and 190% by EB) but not 1OHase. Collectively, the effects of JK in bone and vascular cells closely resemble those of CB or EB. Hence, our data indicate that the novel vitamin D non-calcemic analog JK behaves similarly to other analogs in human cultured cells, thus paving the way to its potential use in vitro and in vivo.