Administration of PTH-(7-84) antagonizes the effects of PTH-(1-84) on bone in rats with moderate renal failure

Endocrinology. 2003 Apr;144(4):1135-8. doi: 10.1210/en.2002-221026.

Abstract

Circulating parathyroid hormone (PTH) is a mixture of PTH-1-84 and carboxy-terminal (C-PTH) fragments. Recently, the "intact" PTH assay was reported to detect not only PTH-(1-84) but also a C-PTH fragment, presumably PTH-(7-84). The purpose of this study was to determine whether PTH-(7-84) antagonizes the PTH-(1-84) effects on bone. Forty-eight rats were thyroparathyroidectomized (TPTX), eight were used as controls and the remaining TPTX rats (10/group) were nephrectomized (Nx) and subsequently given PTH-(1-84), PTH-(7-84), PTH-(1-84) and PTH-(7-84) or no PTH peptide. Another ten rats were sham-operated and served as controls. Administration of PTH-(1-84) brought serum calcium and osteoblast activity i.e., bone turnover, to normal levels. Concomitant administration of PTH-(7-84) abrogated these effects. Administration of PTH-(7-84) alone did not further suppress the levels of serum calcium and bone turnover in these TPTX-Nx rats. Moreover, radioligand binding experiments demonstrate that PTH-(7-84) binds specifically to SaOS cells and is equally displaced by both PTH-(1-84) and (7-84), but only partially displaced by PTH-(1-34). These data indicate that PTH-(7-84) antagonizes PTH-(1-84) effect not only on serum calcium but also on osteoblasts to affect bone turnover.

MeSH terms

  • Animals
  • Body Weight
  • Bone Resorption / drug therapy*
  • Bone Resorption / etiology*
  • Bone Resorption / pathology
  • Calcium / blood
  • Drug Interactions
  • Male
  • Parathyroid Hormone / antagonists & inhibitors
  • Parathyroid Hormone / metabolism
  • Parathyroid Hormone / pharmacology*
  • Parathyroidectomy
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Radioligand Assay
  • Rats
  • Rats, Sprague-Dawley
  • Renal Insufficiency / complications*
  • Thyroidectomy

Substances

  • Parathyroid Hormone
  • Peptide Fragments
  • parathyroid hormone (7-84)
  • Calcium