Regulation by vitamin D metabolites of messenger ribonucleic acid for preproparathyroid hormone in isolated bovine parathyroid cells.

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Abstract
High C concentrations, in parallel with their suppressive effects on parathyroid hormone (PTH) secretion, reversibly and specifically decrease preproPTH mRNA in cultured bovine parathyroid cells. In order to determine whether vitamin D metabolites also regulate the content of preproPTH mRNA, their effects were tested on bovine parathyroid cells in the same culture system. Levels of preproPTH mRNA were determined by dot-blot hybridization or blot hybridization with a labeled cloned c[complementary]DNA probe. Incubation with 1,25-dihyroxycholecalciferol at doses varying from 10 pM to 0.1 .mu.M caused a direct decrease in mRNA down to 50% of control values at 48 h. There was no evidence that 1,25-dihydroxycholecalciferol, even at the highest concentration, had any toxic effects on cell number or viability or on total RNA or RNA synthesis. Levels of .alpha.-actin mRNA did not change in the same experiments, and the suppression of preproPTH mRNA was reversible. When the relative potency of various vitamin D metabolites in suppressing preproPTH mRNA was evaluated, 1,25-dihydroxycholecalciferol > 24,25-dihydroxycholecalciferol > 25-hydroxycholecalciferol > vitamin D3 (cholecalciferol). These effects were highly specific and suggest that vitamin D metabolites play an important role in regulating the production of PTH.
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