Evidence for acute inhibitory effects in vivo of 1 alpha-hydroxycholecalciferol on parathyroid hormone secretion in rats.

In an attempt to elucidate the influence of 1 alpha-hydroxycholecalciferol (1 alpha OHD3) on parathyroid hormone (PTH) secretion, sequential measurements were made of 1) serum calcium and urinary excretion of cAMP in conscious perfused rats, and 2) serum calcium in nephrectomized rats; also, the effects of a single iv injection of 1 alpha OHD3 on these parameters were examined. In conscious perfused rats, 6.25 micrograms/kg (15 nmol/kg) 1 alpha OHD3 reduced the urinary excretion of cAMP (approximately 40% of the initial value; P less than 0.05), which reached a level compatible with that of parathyroidectomized rats at 4 h; this fall was sustained for 24 h. Serum concentrations of calcium (total and ionized) did not change at 6 h, and increased at 24 h. In parathyroidectomized rats which were continuously infused with bovine PTH (0.75 U/h), the vitamin D preparation had no significant effect on the urinary excretion of cAMP. Nephrectomy, followed by an injection of the vehicle (0.05 ml 99.5% ethanol), induced a transient hypercalcemia (13.12 +/- 0.39 mg/dl at 6 h). This hypercalcemic response was prevented by prior parathyroidectomy. Injections of 1.25 and 6.25 micrograms/kg 1 alpha OHD3 caused a significant suppression of the hypercalcemia (P less than 0.05 and P less than 0.1, respectively) in the presence of parathyroid glands, whereas a dose-related hypercalcemic effect was observed in their absence. These results suggest that in rats, 1 alpha OHD3, either directly or most probably after conversion into 1 alpha, 25-dihydroxycholecalciferol, 1) acutely inhibits PTH secretion without causing a significant rise in serum calcium, and 2) suppresses PTH secretion in secondary hyperparathyroidism induced by nephrectomy.