Metabolism of amino- and carboxyl-sequence immunoreactive parathyroid hormone in the bovine: evidence for peripheral cleavage of hormone.

Radioimmunoassays that detect specifically peptide sequences within either the biologically active amino region (N-assay) or inactive carboxyl region (C-assay) of parathyroid hormone (PTH) were used to evaluate the metabolism of PTH during and after infusion and injection of homogeneous (containing less than 0.1% hormonal fragments) intact bovine PTH (bPTH) into calves. During continuous infusions of hormone, when constant blood levels of immunoreactive PTH were reached, a dissociation between the concentrations of amino versus carboxyl immunoreactivity was observed; concentrations of hormone measured by the C-assay rose to a level of approximately three times higher than that measured by the N-assay. Analysis by gel filtration of immunoreactive PTH in plasma samples from calves after injection of hormone showed the rapid disappearance of intact hormone (N- and C-assays) and the appearance of a large fragment detected by the C-assay but not by the N-assay. The hormonal fragment lacked antigenic determinants within the amino peptide sequence required for biologic activity. No additional fragments of PTH were detected by gel filtration using the N- and C-assays. No detectable conversion of intact PTH to hormonal fragments occurred during incubation in vitro in bovine serum. The results are consistent with the concept that PTH is metabolized after entry into the circulation at peripheral sites located outside the vascular space, resulting in the rapid disappearance from blood of intact hormone and the appearance of a biologically inactive hormonal fragment(s). These studies done in calves agree with earlier studies done in dogs and man and point to the existence in mammals of common pathways for the peripheral metabolism of PTH.