TY - JOUR
T1 - Administration of PTH-(7-84) antagonizes the effects of PTH-(1-84) on bone in rats with moderate renal failure
AU - Langub, M. Chris
AU - Monier-Faugere, Marie Claude
AU - Wang, Guodong
AU - Williams, John P.
AU - Koszewski, Nicholas J.
AU - Malluche, Hartmut H.
PY - 2003/4/1
Y1 - 2003/4/1
N2 - 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.
AB - 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.
KW - Bone turnover
KW - Histomorphometry
KW - Parathyroid fragment
KW - Parathyroid hormone
KW - Rats
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U2 - 10.1210/en.2002-221026
DO - 10.1210/en.2002-221026
M3 - Article
C2 - 12639892
AN - SCOPUS:0037388842
SN - 0013-7227
VL - 144
SP - 1135
EP - 1138
JO - Endocrinology
JF - Endocrinology
IS - 4
ER -