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This Article Full Text Full Text (PDF) All Versions of this Article: 297/5/F1192    most recent 00360.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Meir, T. Articles by Naveh-Many, T. PubMed PubMed Citation Articles by Meir, T. Articles by Naveh-Many, T.

Deletion of the vitamin D receptor specifically in the parathyroid demonstrates a limited role for the receptor in parathyroid physiology

¹Minerva Center for Calcium and Bone Metabolism, Nephrology Services, Hadassah Hospital, Jerusalem, Israel; ; ³National Cancer Institute, Bethesda, Maryland; and ; ²Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium

Submitted June 25, 2009 ; accepted in final form August 14, 2009

1,25(OH)₂D₃ decreases parathyroid hormone (PTH) gene transcription through the vitamin D receptor (VDR). Total body VDR^–/– mice have high PTH levels, hypocalcemia, hypophosphatemia, and bone malformations. To investigate PTH regulation by the VDR specifically in the parathyroid, we generated parathyroid-specific VDR knockout mice (PT-VDR^–/–). In both strains, there was a decrease in parathyroid calcium receptor (CaR) levels. The number of proliferating parathyroid cells was increased in the VDR^–/– mice but not in the PT-VDR^–/– mice. Serum PTH levels were moderately but significantly increased in the PT-VDR^–/– mice with normal serum calcium levels. The sensitivity of the parathyroid glands of the PT-VDR^–/– mice to calcium was intact as measured by serum PTH levels after changes in serum calcium. This indicates that the reduced CaR in the PT-VDR^–/– mice enables a physiologic response to serum calcium. Serum C-terminal collagen crosslinks, a marker of bone resorption, were increased in the PT-VDR^–/– mice with no change in the bone formation marker, serum osteocalcin, consistent with a resorptive effect due to the increased serum PTH levels in the PT-VDR^–/– mice. Therefore, deletion of the VDR specifically in the parathyroid decreases parathyroid CaR expression and only moderately increases basal PTH levels, suggesting that the VDR has a limited role in parathyroid physiology.

serum calcium; calcium homeostasis; secondary hyperparathyroidism; calcium receptor; parathyroid hormone