Acute and chronic regulation of circulating PTH: Significance in health and in disease

Circulating human parathyroid hormone (PTH) is immunoheterogenous. It is composed of 80% carboxyl-terminal (C) fragments and of 20% PTH(1–84). This composition contrasts with the biological activity of the hormone, which is only related to PTH(1–84), creating a paradox between circulating PTH composition and PTH bioactivity. PTH molecular forms are either secreted by the parathyroid glands or generated by the peripheral metabolism of PTH(1–84) in the liver. The kidney has a major role in the disposal of C-PTH fragments. Secretion of PTH molecular forms by the parathyroid glands is highly regulated under a variety of clinical conditions, suggesting that C-PTH fragments could exert some biological effects of their own. Recent data suggest that C-PTH fragments can exert biological actions opposite to those of PTH(1–84) by acting on a C-PTH receptor not yet cloned. They can decrease calcium concentration, phosphate excretion, bone resorption and 1,25(OH)2 synthesis. The clinical implications of this new concept are reviewed.