Deletion of the vitamin D receptor specifically in the parathyroid demonstrates a limited role for the receptor in parathyroid physiology.
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.
Meir
Tomer
T
Minerva Center for Calcium and Bone Metabolism, Nephrology Services, Hadassah Hospital, Jerusalem, Israel.
Levi
Ronen
R
Lieben
Liesbet
L
Libutti
Steven
S
Carmeliet
Geert
G
Bouillon
Roger
R
Silver
Justin
J
Naveh-Many
Tally
T
D000818:Animals; D015415:Biomarkers; D001842:Bone and Bones / Q000378:metabolism; D002136:Calcium, Dietary / Q000494:pharmacology; D004247:DNA / Q000235:genetics; D004032:Diet; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D042282:Microdissection; D010280:Parathyroid Glands / Q000473:pathology / Q000502:physiology*; D010281:Parathyroid Hormone / Q000097:blood; D010282:Parathyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000502:physiology*
D015415:Biomarkers; D002136:Calcium, Dietary; D019394:Ki-67 Antigen; D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; D012313:RNA; D004247:DNA