Immunoreactive Parathyroid Hormone in Circulation of Man

WE have reported that parathyroid hormone (PTH) is secreted from the parathyroid in vivo as a polypeptide of eighty-four amino-acids, identical to the hormone stored in the glands (molecular weight of 9,500), but that the hormonal polypeptide is cleaved after it enters the general circulation¹. A large hormonal fragment from this cleavage, with a molecular weight of approximately 7,500, has been identified in the circulation. The fragment differs immunologically from the hormone secreted and extracted from the glands¹. To analyse the biological significance of the metabolism of the hormone and the chemical nature and hormonal activity of the large circulating fragment, we have developed radioimmunoassays that specifically measure the amino-terminal (N-assay) and carboxyl-terminal (C-assay) regions of the hormonal molecule. We now report that much higher concentrations of immunoreactive hormone are found in the general circulation by the C-assay than by the N-assay. The studies with the N-assay indicate that the large fragment has lost a portion of the amino-terminal sequence required for biological activity⁹. Since the fragment is present in much higher concentration than native uncleaved hormone, we must conclude that much of the immunoreactive PTH detected in the circulation is biologically inactive.