Effects of vitamin D metabolites on bovine parathyroid hormone release in vitro

We evaluated the effects of 1 alpha,25-dihydroxycholecalciferol (1,25(OH)2D3), 24R,25-dihydroxycholecalciferol (24,25(OH)2D3), and 25-hydroxycholecalciferol (25(OH)D3) on the release of parathyroid hormone (PTH). Bovine parathyroid tissues were incubated in vitro for 4 h in low-calcium (1.0 mM) medium. 1,25(OH)2D3 ((10(-9)-10(-12)M), 24,25(OH)2D3 (10(-6)-10(-8)M), and 25(OH)D3 (5 X 10(-7)-5 X 10(-9)M) inhibited PTH release. Inhibition by all metabolites was concentration and time dependent. On a molar basis, 1,25(OH)2D3 was the most potent metabolite, being at least 100 times more potent than 24,25(OH)2D3 and 25(OH)D3; 24,25(OH)2D3 was about 5 times more potent than 25(OH)D3 at concentrations producing 65% inhibition. Inhibition by high concentrations of metabolites was evident by 1 h of incubation; inhibition was progressive throughout incubation, and maximal suppression to 30-40% of control occurred during the fourth and final hour of incubation. 1,25(OH)2D3 (10(-11) M), a low concentration that did not inhibit secretion, transiently stimulated release. In conclusion, under conditions of low-calcium-stimulated PTH release, 1,25(OH)2D3, 24,25(OH)2D3, and 25(OH)D3 inhibited PTH release, 1,25(OH)2D3 was the most potent inhibitor.