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

Tomer Meir, Ronen Levi, Liesbet Lieben, Steven Libutti, Geert Carmeliet, Roger Bouillon, Justin Silver, Tally Naveh-Many

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)F1192-F1198
JournalAmerican Journal of Physiology - Renal Physiology
Volume297
Issue number5
DOIs
StatePublished - Nov 1 2009

Keywords

  • Calcium homeostasis
  • Calcium receptor
  • Parathyroid hormone
  • Secondary hyperparathyroidism
  • Serum calcium

ASJC Scopus subject areas

  • Physiology
  • Urology

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