The parathyroid polyhormone hypothesis revisited.
The parathyroid polyhormone hypothesis holds that peptides derived from the metabolism of parathyroid hormone (PTH) (so-called C-terminal fragments) are themselves biologically active and that their effects are mediated by a novel 'C-terminal receptor.' The evidence supporting these assertions is extensive but remains inconclusive. This Commentary focuses on in vivo pharmacology studies that provide information relevant to understanding the physiological significance of C-terminal fragments. The more recent studies of this sort provide compelling evidence that the bioactivity of C-terminal fragments is likely to become physiologically relevant in settings of secondary hyperparathyroidism. In this condition, circulating levels of C-terminal fragments greatly exceed those of PTH. There is convincing evidence that the hypocalcemic effect of C-terminal fragments results from direct actions on the skeleton that inhibit bone resorption. On the other hand, there are few if any results of in vivo studies suggesting a role for C-terminal fragments in more physiological settings, at least when parameters associated with systemic calcium homeostasis are assessed.
Nemeth
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EF
NPS Pharmaceuticals, Toronto, Ontario, Canada. enemeth@npsp.com
D000818:Animals; D001862:Bone Resorption / Q000378:metabolism; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000378:metabolism / Q000473:pathology; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D010280:Parathyroid Glands / Q000378:metabolism* / Q000473:pathology; D010281:Parathyroid Hormone / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D018016:Receptors, Parathyroid Hormone / Q000378:metabolism*
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D018016:Receptors, Parathyroid Hormone