Inhibition of Parathyroid Hormone Secretion by 25-Hydroxycholecalciferol and 24,25-Dihydroxycholecalciferol in the Dog

Abstract

A C T We studied the effects of vitamin D metabolites on parathyroid hormone (PTH) secretion. Test materials were iinjected into the cranial thyroid artery of the dog, and immunoreactive PTH was measured frequently in serum samples from the in- ferior thyroid vein and the femoral vein. This model for the study of secretion had previouslv been vali- dated with the use of known moduilators oni PTH secre- tion. In control experimenits, injection of 100% ethanol, the vehicle in which cholecalciferol (D3) metabolites were suspended, resulted in ino change in PTH secre- tion. Likewise, native vitamin D3, in doses ranging from 250 to 1,250 nlg had Ino effect oIn PTH secretioin. 25- Hydroxycholecalciferol, 25-(OH)D3, in doses of 125- 240 ng, caused complete suppression of PTH secretion. When 24,25-dihydroxycholecalciferol, 24,25-(OH)2D3, was injected in doses of 50-250 ng, suppression of PTH secretion was again complete; in doses of 5 ng, injection of this metabolite resulted in significanit but incomplete suppression of secretion. In doses of 50- 250 ng, 1,25-(OH)2D3 strongly stimulated PTH secre- tion, but in a dose of 5 ng this metabolite had no effects. Injection of e(ual doses of 1,25-(OH)2D3 and 24,25-(OH)2D3 resulted in significant suppression of PTH secretion. Hypocalcemiia-induced stimulation of PTH secretion was suppressed by 24,25-(OH)2D3 while hypercalcemia-induced suppression of PTH secretion was stimulated by 1,25-(OH)2D3. In all experiments showing suppression of PTH secretion, peripheral PTH decreased. Argumeints are presenited for con-