Effect of vitamin D3, 25-hydroxyvitamin D3, and 24,25-dihydroxyvitamin D3 on parathyroid hormone secretion |
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Authors: | Larry K. Cantley John B. Russell Deborah S. Lettieri Louis M. Sherwood |
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Affiliation: | (1) Departments of Medicine and Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, 10461 Bronx, New York |
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Abstract: | Summary The active vitamin D metabolite 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] causes marked suppression of both pre-proparathyroid hormone messenger RNA (pre-proPTH mRNA) and parathyroid hormone (PTH) secretion. These effects are dose dependent and reversible when tested in anin vitro primary tissue culture cell system using normal bovine parathyroid cells. In the current studies, the precursors of 1,25(OH)2D3 and the related metabolite 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], were used in the same culture system to test for possible regulatory effects. The results were compared with identically prepared cells exposed to 1,25(OH)2D3. In short-term studies (30–120 minutes), none of the vitamin D-related compounds produced any effect on PTH secretion. In long-term studies (24–48 hours, using primary tissue culture in the presence of test agents), neither vitamin D3 nor 25(OH)D3 affected PTH secretion or pre-proPTH mRNA over the concentration range 10−11–10−7M. On the other hand, 24,25(OH)2D3 produced significant suppression of both pre-proPTH mRNA (77% of control,P<.01) and PTH secretion (75% of control,P<.005) at 10−7 M. By comparison, 10−11 M 1,25(OH)2D3 produced levels of suppression (25–30%) of both pre-proPTH mRNA and PTH secretion comparable to 10−7 M 24,25(OH)2D3, while even greater suppression (40–50%) occurred at 10−9-10−7 M 1,25(OH)2D3. From these studies, we conclude that vitamin D3 and 25(OH)D3 do not have significant effects on PTH synthesis and secretion over the range of doses tested. Compared with 1,25(OH)2D3, 24,25(OH)2D3 exhibits mild suppression at pharmacologic concentrations. The effect of 24,25(OH)2D3 prabably occurs through weak interaction of 24,25(OH)2D3 with the 1,25(OH)2D3 receptor. |
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Keywords: | 1,25-Dihydroxyvitamin D3 24,25-Dihydroxyvitamin D3 Pre-proparathyroid hormone mRNA Secretion Tissue culture |
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