Administration of PTH-(7-84) Antagonizes the Effects of PTH-(1-84) on Bone in Rats with Moderate Renal Failure

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) antagoniz...

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Published in:Endocrinology (Philadelphia) 2003-04, Vol.144 (4), p.1135-1138
Main Authors: Langub, M. Chris, Monier-Faugere, Marie-Claude, Wang, Guodong, Williams, John P, Koszewski, Nicholas J, Malluche, Hartmut H
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Body Weight
Bone Resorption - drug therapy
Bone Resorption - etiology
Bone Resorption - pathology
Calcium - blood
Drug Interactions
Fundamental and applied biological sciences. Psychology
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
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Summary: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.
ISSN:0013-7227
1945-7170
DOI:10.1210/en.2002-221026