Inhibition by 1,25 dihydroxycholecalciferol of hormonal secretion of rat parathyroid gland in organ culture.

The effect of vitamin D metabolites on parathyroid hormone secretion was studied using rat parathyroid gland cultured in basal medium Eagle containing 5% serum obtained from thyroparathyroidectomized rat, 1 mM magnesium, and calcium concentration varying from 0.75-2.25 mM, and radioimmunoassay for rat parathyroid hormone (rPTH). 1.25 dihydroxycholecalciferol (1,25(OH)2D3), 5 X 10(-10)-2.5 X 10(-8) M, consistently decreased rPTH secretion in dose-related manner; the effect reached steady state after 24 h in vitro addition of 1,25(OH)2D3 and was also observed at different medium calcium concentrations (0.75, 1.25, 1.75 mM). Comparison of dose-responses for inhibitory activity of some vitamin D metabolites on rPTH secretion showed: 1,25(OH)2D3 = 1,24,25(OH)3D3 greater than 1 alpha OHD3 greater than 25 OHD3. Cholecalciferol (10(-5) M), 24,25-dihydroxy-cholecalciferol (10(-8)-10(-6) M) and 25,26-dihydroxy-cholecalciferol (5 X 10(-9)-5 X 10(-7) M) did not inhibit rPTH secretion. Analysis of structural activity relation of vitamin D metabolites studied indicated that 1 alpha or pseudo-1 alpha hydroxylated metabolites or analogs were active in inhibiting rPTH secretion, while, non-1 alpha hydroxylated metabolites were without or were weakly inhibitory only at very high concentrations. This study provides further evidence for a direct role of 1,25(OH)2D3 on a negative feedback loop for regulation of parathyroid gland function.