Carboxyl-terminal parathyroid hormone fragments: role in parathyroid hormone physiopathology.
OBJECTIVE
Carboxyl-terminal parathyroid hormone (C-PTH) fragments constitute 80% of circulating PTH. Since the first 34 amino acids of the PTH structure are sufficient to explain PTH classical biological effects on the type I PTH/PTHrP receptor and since C-PTH fragments do not bind to this receptor, they have long been considered inactive. Recent data suggest the existence of a C-PTH receptor through which C-PTH fragments exert biological effects opposite to those of human PTH(1-84) on the type I PTH/PTHrP receptor. This is why a lot of attention has been paid to these fragments recently.


RESULTS
In vivo, synthetic C-PTH fragments are able to decrease calcium concentration, to antagonize the calcemic response to human PTH(1-34) and human PTH(1-84) and to decrease the high bone turnover rate induced by human PTH(1-84). In vitro, they inhibit bone resorption, promote osteocyte apoptosis and exert a variety of effects on bone and cartilaginous cells. These effects are opposite to those of human PTH(1-84) on the PTH/PTHrP type I receptor. This suggests that the molecular forms of circulating PTH may control bone participation in calcium homeostasis via two different receptors. Clinically, the accumulation of C-PTH fragments in renal failure patients may cause PTH resistance and may be associated with adynamic bone disease. Rare parathyroid tumors, without a set point error, overproduce C-PTH fragments. The implication of C-PTH fragments in osteoporosis is still to be explored.


CONCLUSIONS
C-PTH fragments represent a new field of investigation in PTH biology. More studies are necessary to disclose their real importance in calcium and bone homeostasis in health and disease.
D'Amour
Pierre
P
Centre de recherche, Centre hospitalier de l'Université de Montréal, Hôpital Saint-Luc et Département de médecine, Université de Montréal, Montréal, Québec, Canada. rechcalcium.chum@ssss.gouv.qc.ca
Brossard
Jean-Hugues
JH
D000818:Animals; D006801:Humans; D006961:Hyperparathyroidism / Q000097:blood*; D006962:Hyperparathyroidism, Secondary / Q000097:blood*; D010024:Osteoporosis / Q000097:blood*; D010281:Parathyroid Hormone / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*
D010281:Parathyroid Hormone; D010446:Peptide Fragments; C023443:carboxyl-terminal parathyroid hormone