G. P. Mayer

Parathyroid hormone secretion in vivo. Demonstration of a calcium-independent nonsuppressible component of secretion.

The response of normal bovine parathyroid glands to hypercalcemia was assessed in vivo by radioimmunoassay of immunoreactive parathyroid hormone concentrations in parathyroid effluent blood obtained by surgical cannulation of both anesthetized and nonanesthetized calves. Hypercalcemia was induced for periods of 0.3-35 h by intravenous infusion of a solution of calcium chloride. Assessment of immunoreactivity in effluent and peripheral blood included measurements of selected samples by use of a radioimmunoassay specific for a site residing in the biologically active portion of the hormone molecule. In all instances, the concentration of immunoreactive parathyroid hormone in hypercalcemic venous effluent from a superior parathyroid gland exceeded that of the peripheral blood. Failure of hypercalcemia to suppress completely secretion by normal parathyroids indicates that a portion of parathyroid hormone secretion occurs independent of blood calcium concentration. Consequently, continued parathyroid hormone secretion despite hypercalcemia can no longer be regarded as a unique feature of parathyroid neoplasia.

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.

Dextran-charcoal and dioxane phase separation methods in the radioimmunoassays for parathyroid hormone and calcitonin.

Dioxane precipitation and dextran-charcoal adsorption were used to separate free from bound /sup 125/I-labelled hormone in the radioimmunoassays of calcitonin and parathyroid hormone. Changes in the fraction of bound radioactivity, independent of hormone concentrations, were seen with changes in temperature, plasma concentration, time of standing, and amount of dioxane or dextran-charcoal added. Characterization of these variables affecting bound radioactivity, and careful standardization of the conditions of phase separation, indicate that dioxane precipitation is a satisfactory method for the calcitonln immunoassay while dextran-charcoal adsorption provides the most reliable results in the parathyroid hormone immunoassay. (INIS)

Plasma calcitonin in the bovine species.

Summary Calcitonin (CT) was measured by radioimmunoassay in plasma samples from 169 bo vines of varying age, sex, and calcium diets. Younger animals had higher plasma CT than older animals. Bulls had higher plasma CT than cows or steers. Older bulls on a high calcium diet had higher plasma CT than those on a low calcium diet whereas there was no significant difference in plasma calcium between them. These studies demonstrate that age, sex, and dietary calcium can influence plasma CT in the bovine.