1,25(OH)₂-vitamin D₃ reduces spontaneous and hypocalcemia-stimulated pulsatile component of parathyroid hormone secretion

To investigate the effects of 1,25(OH)₂-vitamin D₃ (1,25(OH)₂D₃) on pulsatile parathyroid hormone (PTH) release, minute-to-minute intact PTH secretion was examined in nine healthy adults under baseline conditions and during hypocalcemia (sodium citrate clamp) before and after 5 d of oral 1,25(OH)₂D₃ treatment (1 μg/d). In addition, acute effects of 1,25(OH)₂D₃ were examined by a single intravenous bolus of 2 μg of 1,25(OH)₂D₃. Pulsatile and tonic PTH secretion rates were calculated by the multiparameter deconvolution technique. During baseline, 68% of circulating PTH was attributable to tonic, and 32% to pulsatile, secretion. During induction of hypocalcemia, a selective increase in pulsatile secretion (+1100%), mediated by a combined increase in burst frequency and burst mass, was observed. During the subsequent steady-state hypocalcemic period, burst frequency and mass decreased and tonic secretion increased to 3 times the baseline level. Intravenous 1,25(OH)₂D₃ did not affect the temporal pattern of PTH secretion. In contrast, oral 1,25(OH)₂D₃ decreased baseline plasma PTH by 30% without a detectable change in Ca²⁺. This suppression was accounted for mainly by a decrease in PTH burst frequency. During hypocalcemia induction, a significantly lower (30%) increase in burst mass occurred compared with the pretreatment study. During steady-state hypocalcemia, PTH burst mass (-45%) and pulsatile (-50%) and total (-35%) secretion rate were lower than before treatment. In conclusion, acute hypocalcemia selectively increases pulsatile PTH release by stimulating both burst frequency and mass via a Ca²⁺ rate-sensitive mechanism. Oral 1,25- (OH)₂D₃ suppresses pulsatile baseline PTH release and reduces the pulsatile secretory capacity of the parathyroids during a hypocalcemic stimulus.