Regulation of 1,25-dihydroxyvitamin D₃ receptor gene expression by 1,25-dihydroxyvitamin D₃ in the parathyroid in vivo

1,25-Dihydroxyvitamin D₃ (1,25(OH)₂D₃) dramatically decreases parathyroid hormone (PTH) gene transcription. We have now studied the effect of 1,25(OH)₂D₃ on the 1,25(OH)₂D receptor (VDR) in the parathyroid in vivo. Rats were injected with 1,25(OH)₂D₃ and the parathyroid-thyroid tissue analyzed for PTHmRNA and VDRmRNA. 1,25(OH)₂D₃ (50 and 100 pmol ip) decreased PTHmRNA at 6 h with a maximum at 48 h (< 4% of basal), whereas VDRmRNA was increased only after 6 h with a 1.7-fold increase at 24 h. VDRmRNA levels peaked at 25 pmol 1,25(OH)₂D₃ with a twofold increase. Serum calcium did not affect VDRmRNA. Parathyroid VDRmRNA ran at 2.2 and 4.4 kb, whereas duodenum VDRmRNA had a single band, all of which increased after 1,25(OH)₂D₃. Weanling rats on a vitamin D-deficient diet for 3 wk had a more intense 2.2-kb transcript, whereas vitamin D-replete rats had a more intense 4.4-kb band. Dispersed parathyroid-thyroid cells were separated by a flow cytometry (FACS) into a parathyroid cell peak containing PTHmRNA and a second peak with cells positive for thyroglobulin mRNA and calcitonin mRNA. VDRmRNA was concentrated in the parathyroid cell peak. In situ hybridization of parathyroid-thyroid and duodenum for VDRmRNA showed its localization to the parathyroid cells and the duodenal mucosa. Therefore, the VDRmRNA in the parathyroid-thyroid tissue represents predominantly parathyroid cell and not C-cell VDRmRNA which is also a 1,25(OH)₂D₃ target organ. The increased VDR gene expression in the parathyroid cell would amplify the effect of 1,25(OH)₂D₃ to decrease PTH gene transcription.