Evidence for Acute Inhibitory Effects in Vivo of la Hydroxycholecalciferol on Parathyroid Hormone Secretion in Rats*

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Abstract
In an attempt to elucidate the influence of 1αhydroxycholecalciferol (lαOHD3) 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 lαOHD3 on these parameters were examined. In conscious perfused rats, 6.25 jug/kg (15 nmol /kg) lαOHD3 reduced the urinary excretion of cAMP (∼40% of the initial value; P < 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 μg/kg lαOHD3 caused a significant suppression of the hypercalcemia (P < 0.05 and P < 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, lαOHD3, either directly or most probably after conversion into lα25-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.