Peripheral metabolism of parathyroid hormone in patients with primary hyperparathyroidism as judged by immunological and biological studies.

The present study characterizes the immunological and biological activity of circulating forms of parathyroid hormone (PTH) in patients with primary hyperparathyroidism. In addition, the rate of elimination of intravenously injected 125I-labelled bovine parathyroid hormone (125I-bPTH) was studied in patients with this disease before and after operation. The different molecular forms of serum PTH were characterized by gel chromatography followed by radioimmunoassay employing two antisera with specificities directed against the N-terminal and mid-region part of the peptide, respectively. The major part of immunoreactive PTH (iPTH; on the average above 50%) eluted corresponding to fragments with a molecular size about 7,500 daltons in both radioimmunoassays. Specific immunoreactivity coeluting with the intact hormone represented 9-15%. The biological activity of hyperparathyroid serum after gel chromatography was tested in a hormone-sensitive rat kidney adenylyl cyclase assay system. The basal and PTH-stimulated adenylyl cyclase activity (half-maximal) stimulation at 5 micrograms/l or 0.6 nM) was dependent on Mg2+ and ATP. Maximal responses to PTH, calcitonin, and prostaglandin E2 were 50-200% above basal activity and were obtained in the presence of both GTP and Gpp(NH)p (5 X 10(-4) M). Serum from patients with hyperparathyroidism and PTH extracted from parathyroid tissue stimulated the adenylyl cyclase in a dose-dependent manner, as did the chromatographic fraction representing the intact hormone. Elimination of 125I-bPTH from circulation after intravenous injection to patients with this disease suggested that the hormone, but not its degradation products, were removed more rapidly before than after successful surgery. We conclude that the major part of circulating iPTH in patients with primary hyperparathyroidism is unable to stimulate the rat kidney adenylyl cyclase, and that the biological PTH activity is represented by the intact hormone (15% or less of total iPTH). These patients degrade more rapidly the injected 125I-bPTH and this mechanism introduces a new concept to protect target cells against excessive hormone action.