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- Title
Parathyroid hormone fragments inhibit active hormone and hypocalcemia-induced 1,25(OH)2D synthesis.
- Authors
Usatii M; Rousseau L; Demers C; Petit J; Brossard J; Gascon-Barré M; Lavigne JR; Zahradnik RJ; Nemeth EF; D'Amour P; Usatii, M; Rousseau, L; Demers, C; Petit, J-L; Brossard, J-H; Gascon-Barré, M; Lavigne, J R; Zahradnik, R J; Nemeth, E F; D'Amour, P
- Abstract
Carboxyl (C)-terminal fragments of parathyroid hormone (PTH) oppose the calcemic, phosphaturic, and bone-resorbing effects of active hormone. To study the action of these fragments on 1,25(OH)(2)D (1,25-dihydroxyvitamin D) synthesis, we infused parathyroidectomized rats with human or rat active 1-34 or 1-84 PTH at doses selected to produce similar calcemic responses. Human active PTH influenced neither phosphate nor 1,25(OH)(2)D concentrations. However, active 1-34 rat PTH decreased phosphate to the same level as vehicle-treated rats and increased 1,25(OH)(2)D to very high levels, whereas active 1-84 PTH decreased phosphate but maintained 1,25(OH)(2)D. As the latter effect could have been due to C-terminal fragment generation during its metabolic breakdown, we infused a mixture of rat C-terminal fragments alone or with rat 1-34. The C-terminal fragments decreased 1,25(OH)(2)D and prevented hypocalcemic-induced 1,25(OH)(2)D synthesis. When infused with active rat 1-34, they lowered the 1,25(OH)(2)D level to that seen with intact rat 1-84. The C-terminal fragments did not influence either basal or rat 1-34- or 1-84-induced CYP27B1 mRNA levels, suggesting that their inhibitory effects on 1,25(OH)(2)D synthesis appears to be post-transcriptional.
- Publication
Kidney International, 2007, Vol 72, Issue 11, p1330
- ISSN
0085-2538
- Publication type
journal article
- DOI
10.1038/sj.ki.5002532