期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2005
卷号：102
期号：13
页码：4724-4728
DOI：10.1073/pnas.0501312102
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The vitamin D receptor (VDR) is a nuclear transcription factor responsible for mediating the biological activities of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Renal and parathyroid gland VDR content is an important factor in calcium homeostasis, vitamin D metabolism, and the treatment of secondary hyperparathyroidism and renal osteodystrophy. In these tissues, VDR expression is highly regulated by the calcium and vitamin D status. Although 1,25(OH)2D3 up-regulates VDR expression, hypocalcemia and vitamin D deficiency result in drastically reduced expression of the receptor. The generation of 25-hydroxyvitamin D3-1{alpha}-hydroxylase-null mice, which are incapable of endogenously producing 1,25(OH)2D3, has allowed us to investigate the influence of parathyroid hormone (PTH) on VDR expression independent of PTH-mediated increases in 1,25(OH)2D3. Administration of human PTH (1-34) (110 {micro}g/kg per day) for 48 h reduced renal VDR levels from 515 to 435 fmol/mg protein (15%, P < 0.03) in wild-type mice. In the 25-hydroxyvitamin D3-1{alpha}-hydroxylase-null mice, PTH administration strongly reduced renal VDR levels, from 555 to 394 fmol/mg protein (29%, P < 0.001). These results demonstrate that PTH is a potent down-regulator of VDR expression in vivo.
