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Vitamin D–Independent Therapeutic Effects of Extracellular Calcium in a Mouse Model of Adult‐Onset Secondary Hyperparathyroidism
Author(s) -
Weber Karin,
Zeitz Ute,
Bergow Claudia,
Hirmer Sieglinde,
Schüler Christiane,
Erben Reinhold G
Publication year - 2009
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.0080904
Subject(s) - calcitriol receptor , endocrinology , medicine , secondary hyperparathyroidism , vitamin d and neurology , hyperparathyroidism , parathyroid chief cell , calcium , parathyroid hormone , parathyroid gland , extracellular , calcium sensing receptor , chemistry , biology , biochemistry
Cell proliferation and PTH secretion in the parathyroid gland are known to be regulated by vitamin D and extracellular calcium. Here, we examined the vitamin D–independent effects of correction of extracellular calcium in an adult‐onset secondary hyperparathyroidism (sHPT) model, using mice with a nonfunctioning vitamin D receptor (VDR). Wildtype and homozygous VDR mutant mice were kept on a rescue diet (RD) containing 2% calcium (Ca), 1.25% phosphorus (P), and 20% lactose until they were 4 mo or 1 yr of age. Subsequently, 4‐mo‐old mice were switched to a challenge diet (CD) containing the following: 0.5% Ca, 0.4% P, and 0% lactose. After 2 mo on the CD, groups of VDR mutant mice were either fed CD, a normal mouse chow with 0.9% Ca, 0.7% P, and 0% lactose, or the RD for another 3 mo. Feeding the RD protected VDR mutants against sHPT over 1 yr, showing that vitamin D is not essential for long‐term control of the function and proliferation of parathyroid cells. When 4‐mo‐old VDR mutants were switched from the RD to the CD for 2 mo, they developed severe sHPT associated with hypertrophy and hyperplasia of parathyroid glands and profound bone loss. Subsequent feeding of the RD during a 3‐mo therapy phase fully corrected sHPT, reduced chief cell proliferation, and reduced maximum parathyroid gland area by 25% by cell atrophy. There was no evidence of RD‐induced chief cell apoptosis. We conclude that signaling by the calcium‐sensing receptor regulates chief cell function and size in the absence of signaling through the VDR.