Inhibition of parathyroid hormone secretion by 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol in the dog.
We studied the effects of vitamin D metabolites on parathyroid hormone (PTH) secretion. Test materials were injected into the cranial thyroid artery of the dog, and immunoreactive PTH was measured frequently in serum samples from the inferior thyroid vein and the femoral vein. This model for the study of secretion had previously been validated with the use of known modulators on PTH secretion. In control experiments, injection of 100% ethanol, the vehicle in which cholecalciferol (D(3)) metabolites were suspended, resulted in no change in PTH secretion. Likewise, native vitamin D(3), in doses ranging from 250 to 1,250 ng had no effect on PTH secretion. 25-Hydroxycholecalciferol, 25-(OH)D(3), in doses of 125-240 ng, caused complete suppression of PTH secretion. When 24,25-dihydroxycholecalciferol, 24,25-(OH)(2)D(3), 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 significant but incomplete suppression of secretion. In doses of 50-250 ng, 1,25-(OH)(2)D(3) strongly stimulated PTH secretion, but in a dose of 5 ng this metabolite had no effects. Injection of equal doses of 1,25-(OH)(2)D(3) and 24,25-(OH)(2)D(3) resulted in significant suppression of PTH secretion. Hypocalcemia-induced stimulation of PTH secretion was suppressed by 24,25-(OH)(2)D(3) while hypercalcemia-induced suppression of PTH secretion was stimulated by 1,25-(OH)(2)D(3). In all experiments showing suppression of PTH secretion, peripheral PTH decreased. Arguments are presented for considering the suppressive effects of D(3) metabolites as physiologic modulators. However, this stimulating effect of 1,25-(OH)(2)D(3) occurred only in pharmacologic doses and hence probably has no physiologic relevance.
D000818:Animals; D003864:Depression, Chemical; D004100:Dihydroxycholecalciferols / Q000494:pharmacology*; D004285:Dogs; D004347:Drug Interactions; D005260:Female; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D006934:Hypercalcemia / Q000378:metabolism; D006996:Hypocalcemia / Q000378:metabolism; D008297:Male; D010281:Parathyroid Hormone / Q000378:metabolism*; D012636:Secretory Rate / Q000187:drug effects
D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D010281:Parathyroid Hormone