Parathyroid hormone decreases renal vitamin D receptor expression in vivo.
The vitamin D receptor (VDR) is a nuclear transcription factor responsible for mediating the biological activities of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. 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)(2)D(3) up-regulates VDR expression, hypocalcemia and vitamin D deficiency result in drastically reduced expression of the receptor. The generation of 25-hydroxyvitamin D(3)-1alpha-hydroxylase-null mice, which are incapable of endogenously producing 1,25(OH)(2)D(3), has allowed us to investigate the influence of parathyroid hormone (PTH) on VDR expression independent of PTH-mediated increases in 1,25(OH)(2)D(3). Administration of human PTH (1-34) (110 microg/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 D(3)-1alpha-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.
Healy
Kevin D
KD
Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA.
Vanhooke
Janeen L
JL
Prahl
Jean M
JM
DeLuca
Hector F
HF
D000818:Animals; D002118:Calcium / Q000097:blood; D017931:DNA Primers; D015536:Down-Regulation / Q000187:drug effects*; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010281:Parathyroid Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010758:Phosphorus / Q000097:blood; D018167:Receptors, Calcitriol / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013054:Spectrophotometry, Atomic
D017931:DNA Primers; C470125:PTH protein, human; D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; D010758:Phosphorus; D002118:Calcium