To elucidate whether PTH(7-84), a degradation product of PTH(1-84), which inhibits PTH(1-84)-induced hone 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)(2)D-3 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-OHD3 (10(6) M), 1,25-(OH)(2)D-3 was determined. PTH(1-34) stimulated the conversion of 25-OHD3 to 1,25-(OH)(2)D-3, and PTH(7-84) dose-dependently inhibited this process. Real-time PCR revealed that PTH(1-34) increased the expression level of 1 alpha-hydroxylase mRNA, whereas PTH(7-84) did not affect the expression level 1 alpha 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 1 PTH/PTHrP receptor. This may at least partly account for the decreased serum level of 1,25-(OH)(2)D in patients with severe primary hyperparathyroidism with renal failure. (c) 2009 Elsevier Inc. All rights reserved.