Vitamin D receptor agonists (VDRAs) directly suppress
parathyroid hormone (PTH)
mRNA expression. Different VDRAs are known to have differential effects on serum
calcium (Ca), which may also affect serum PTH levels since serum Ca regulates PTH secretion mediated by the
Ca-sensing receptor (CaSR). In this study, we compared the effects of
paricalcitol and
doxercalciferol on regulating serum Ca and PTH, and also the expression of PTH, VDR, and CaSR
mRNA. The 5/6 nephrectomized (NX) Sprague-Dawley rats on a normal or
hyperphosphatemia-inducing diet were treated with vehicle,
paricalcitol, or
doxercalciferol for two weeks. Both drugs at the tested doses (0.042-0.33 mug/kg) suppressed PTH
mRNA expression and serum PTH effectively in the 5/6 NX rats, but
paricalcitol was less potent in raising serum Ca than
doxercalciferol. In pig parathyroid cells,
paricalcitol and the active form of
doxercalciferol induced VDR translocation from the cytoplasm into the nucleus, suppressed PTH
mRNA expression and inhibited cell proliferation in a similar manner, although
paricalcitol induced the expression of CaSR
mRNA more effectively. The multiple effects of VDRAs on modulating serum Ca, parathyroid cell proliferation, and the expression of CaSR and PTH
mRNA reflect the complex involvement of the
vitamin D axis in regulating the
mineral homeostasis system.