1,25-Dihydroxyvitamin D3Suppresses Parathyroid Hormone Secretion from Bovine Parathyroid Cells in Tissue Culture*

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Abstract
To determine whether 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] regulates PTH secretion, we have tested its effects in both short term incubations (30-120 min) and long term primary cell cultures (24-96 h) of bovine parathyroid cells. In short term incubations, 10-11-10-7 M 1,25-(OH)2D3 had no consistent effect on PTH secretion. In primary cultures of bovine parathyroid cells, significant suppression of PTH secretion occurred, as measured by both N-terminal and C-terminal PTH assays. Suppression of PTH secretion was dose dependent when 10-11, 10-9, and 10-7 M 1,25-(OH)2D3 were tested for 48 h in culture, and the effects of 10-7 M 1,25-(OH)2D3 were noted as early as 24 h. Reversal of suppression of PTH secretion was observed after an additional 48 h in the absence of 1,25-(OH)2D3. Other studies from our laboratory have demonstrated that 1,25-(OH)2D3 suppresses levels of pre-pro-PTH mRNA in cultured bovine parathyroid cells, and we found a strong correlation at 48 h between the decrease in PTH release and that in mRNA. We conclude that (1) 1,25-(OH)2D3 suppresses PTH secretion rates in a dose-dependent manner in cells grown for 24-48 h in culture, but does not have a significant effect on short term PTH release (30-120 min); (2) cultured cells exhibiting suppression by 1,25-(OH)2D3 demonstrate nearly full recovery of PTH secretion after an additional 48 h in the absence of added 1,25-(OH)2D3; and (3) PTH secretion closely parallels levels of pre-pro-PTH mRNA in cultured cells, suggesting that the observed effects of PTH secretion reflect, at least in part, suppression of synthesis of PTH by 1,25-(OH)2D3.