PTH(7-84) inhibits PTH(1-34)-induced 1,25-(OH)2D3 production in murine renal tubules.
To elucidate whether PTH(7-84), a degradation product of PTH(1-84), which inhibits PTH(1-84)-induced bone resorption, also exerts an antagonistic effect on the kidney, we studied the effect of PTH(7-84) on PTH(1-34)-induced production of 1,25-(OH)2D3 in primary cultured murine renal tubules. Neonatal mouse renal tubules cultured in serum-free MEM for 7 days were treated with PTH(1-34) and/or PTH(7-84). Three hours after addition of 25-OHD(3) (10(-6) M), 1,25-(OH)2D3 was determined. PTH(1-34) stimulated the conversion of 25-OHD3 to 1,25-(OH)2D3, and PTH(7-84) dose-dependently inhibited this process. Real-time PCR revealed that PTH(1-34) increased the expression level of 1alpha-hydroxylase mRNA, whereas PTH(7-84) did not affect the expression level 1alpha or 24-hydroxylase mRNA. These in vitro data suggest that PTH(7-84) elicits an antagonistic effect in renal tubules through receptors different from the type I PTH/PTHrP receptor. This may at least partly account for the decreased serum level of 1,25-(OH)2D in patients with severe primary hyperparathyroidism with renal failure.
Nakajima
Kishiko
K
Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical University, Kawada-cho 8-1, Shinjuku-ku, Tokyo 162-8666, Japan.
Nohtomi
Kyoko
K
Sato
Masayo
M
Takano
Kazue
K
Sato
Kanji
K