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Title: Deletion of the vitamin D receptor specifically in the parathyroid demonstrates a limited role for the receptor in parathyroid physiology
Authors: Meir, Tomer ×
Levi, Ronen
Lieben, Liesbet
Libutti, Steven
Carmeliet, Geert
Bouillon, Roger
Silver, Justin
Naveh-Many, Tally #
Issue Date: Nov-2009
Publisher: American Physiological Society
Series Title: American Journal of Physiology. Renal Physiology vol:297 issue:5 pages:F1192-F1198
Abstract: Meir T, Levi R, Lieben L, Libutti S, Carmeliet G, Bouillon R, Silver J, Naveh-Many T. Deletion of the vitamin D receptor specifically in the parathyroid demonstrates a limited role for the receptor in parathyroid physiology. Am J Physiol Renal Physiol 297: F1192-F1198, 2009. First published August 19, 2009; doi: 10.1152/ajprenal.00360.2009.-1,25(OH)(2)D-3 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.
ISSN: 1931-857X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
× corresponding author
# (joint) last author

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