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) 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.
Langub
M Chris
MC
Division of Nephrology, Bone and Mineral Metabolism, Department of Medicine, University of Kentucky, Lexington Kentucky 40536, USA. clangub@uky.edu
Monier-Faugere
Marie-Claude
MC
Wang
Guodong
G
Williams
John P
JP
Koszewski
Nicholas J
NJ
Malluche
Hartmut H
HH
D000818:Animals; D001835:Body Weight; D001862:Bone Resorption / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D002118:Calcium / Q000097:blood; D004347:Drug Interactions; D008297:Male; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D016105:Parathyroidectomy; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000150:complications*; D013965:Thyroidectomy
D010281:Parathyroid Hormone; D010446:Peptide Fragments; C414937:parathyroid hormone (7-84); D002118:Calcium