TY - JOUR
T1 - The prostate 25-hydroxyvitamin D-1α-hydroxylase is not influenced by parathyroid hormone and calcium
T2 - Implications for prostate cancer chemoprevention by vitamin D
AU - Young, Michael V.
AU - Schwartz, Gary G.
AU - Wang, Lilin
AU - Jamieson, Daniel P.
AU - Whitlatch, Lyman W.
AU - Flanagan, John N.
AU - Lokeshwar, Balakrishna L
AU - Holick, Michael F.
AU - Chen, Tai C.
N1 - Funding Information:
The authors thank Kelly Persons for maintaining the cell cultures used in the study. This work was supported in part by grants MO1RR00533 from NIH, 4118PP1017 and 41211159016 from The Commonwealth of Massachusetts, and US Army DAMD (to T.C.C.), RO1CA68565 and R03CA85750 from NIH (to G.G.S.), and R01 CA63108 from NIH and US Army DAMD 17/98/8526 (to B.L.L.).
PY - 2004/6
Y1 - 2004/6
N2 - The hormonal form of vitamin D, 1α,25-dihydroxyvitamin D [1α,25(OH)2D] promotes the differentiation and inhibits the proliferation, invasiveness and metastasis of prostate cells. However, 1α,25(OH)2D is not suitable as a chemo-preventive agent because its administration can cause hypercalcemia. Serum levels of 1α,25(OH)2D are tightly regulated by the renal enzyme, 25-hydroxyvitamin D-1α-hydroxylase (1α-OHase), which synthesizes 1α,25(OH)2D from the prohormone, 25-hydroxyvitamin D [25(OH)D]. Normal prostate epithelial cells in primary culture, as well as several prostate cancer cell lines, also express 1α-OHase and synthesize the hormone intracellularly. We now investigated the regulation of the prostate 1α-OHase by the three most important regulators of the renal 1α-OHase: calcium, 1α,25(OH)2D and parathyroid hormone (PTH). The 1α-OHase activity in the primary cultures of prostate epithelial cells was inhibited by 1α,25(OH 2D3 at 10 and 100 nM, whereas PTH at 10 and 100 nM had no significant effect. Calcium at 1.2 and 2.4 mM had no significant effect on the enzyme activity in the PZ-HPV-7 cell line, a prostate epithelial cell line derived from normal prostate tissue. Conversely, 1.2 or 2.4 mM calcium markedly inhibited 1α-OHase activity in a human kidney cell line used as a positive control. Furthermore, PTH at 100 nM and calcium at 1.2 and 2.4 mM had no effect on the 1α-OHase gene promoter activity in prostate cells, whereas the promoter activity was inhibited 48 ± 5% by 100 nM 1α,25(OH 2D3. Our findings suggest that, unlike the renal enzyme, the prostate 1α-OHase appears to be largely unregulated by serum levels of PTH and calcium. These findings support the hypothesis that vitamin D or 25(OH)D may be useful as chemopreventive agents for prostate cancer because their administration should cause an increased synthesis of 1α,25(OH)2D within prostate cells.
AB - The hormonal form of vitamin D, 1α,25-dihydroxyvitamin D [1α,25(OH)2D] promotes the differentiation and inhibits the proliferation, invasiveness and metastasis of prostate cells. However, 1α,25(OH)2D is not suitable as a chemo-preventive agent because its administration can cause hypercalcemia. Serum levels of 1α,25(OH)2D are tightly regulated by the renal enzyme, 25-hydroxyvitamin D-1α-hydroxylase (1α-OHase), which synthesizes 1α,25(OH)2D from the prohormone, 25-hydroxyvitamin D [25(OH)D]. Normal prostate epithelial cells in primary culture, as well as several prostate cancer cell lines, also express 1α-OHase and synthesize the hormone intracellularly. We now investigated the regulation of the prostate 1α-OHase by the three most important regulators of the renal 1α-OHase: calcium, 1α,25(OH)2D and parathyroid hormone (PTH). The 1α-OHase activity in the primary cultures of prostate epithelial cells was inhibited by 1α,25(OH 2D3 at 10 and 100 nM, whereas PTH at 10 and 100 nM had no significant effect. Calcium at 1.2 and 2.4 mM had no significant effect on the enzyme activity in the PZ-HPV-7 cell line, a prostate epithelial cell line derived from normal prostate tissue. Conversely, 1.2 or 2.4 mM calcium markedly inhibited 1α-OHase activity in a human kidney cell line used as a positive control. Furthermore, PTH at 100 nM and calcium at 1.2 and 2.4 mM had no effect on the 1α-OHase gene promoter activity in prostate cells, whereas the promoter activity was inhibited 48 ± 5% by 100 nM 1α,25(OH 2D3. Our findings suggest that, unlike the renal enzyme, the prostate 1α-OHase appears to be largely unregulated by serum levels of PTH and calcium. These findings support the hypothesis that vitamin D or 25(OH)D may be useful as chemopreventive agents for prostate cancer because their administration should cause an increased synthesis of 1α,25(OH)2D within prostate cells.
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U2 - 10.1093/carcin/bgh082
DO - 10.1093/carcin/bgh082
M3 - Article
C2 - 14729578
AN - SCOPUS:3042738165
SN - 0143-3334
VL - 25
SP - 967
EP - 971
JO - Carcinogenesis
JF - Carcinogenesis
IS - 6
ER -
