Effects of Plasma Calcium Concentration on the Relative Proportion of Hormone and Carboxyl Fragments in Parathyroid Venous Blood*

Abstract

The molecular nature of immunoreactivity in parathyroid venous blood, which was collected from anesthetized calves by surgical cannulation, was examined by gel filtration and RIAs with specificity for either the amino (N assay) or carboxyl (C assay) end of the hormone molecule. All samples contained immunoreactivity which eluted from the gel column (Bio-Gel P-100; 45 × 1.2 cm) coincident with radioiodinated purified parathyroid hormone (84 amino acids). This material reacted in both N and C assays. In addition to this, the effluent plasma immunoreactivity contained another component which eluted from the column after the radiolabeled hormone and was recognized only by the C assay. Very little of the latter type of material was found in hypocalcemic samples, but it represented an increased proportion of the total immunoreactivity in normocalcemic samples and this material was the predominant form of immunoreactivity in hypercalcemic samples. RIA of a series of samples of parathyroid venous plasma, collected sequentially from five anesthetized neonatal calves during induced alterations of plasma calcium concentration, revealed that the ratio of the concentration of C-reactive material to that of N-reactive material varied with plasma calcium concentration. The C:N ratio (ratio of carboxyl to amino immunoreactivity) of these samples increased from a value of about 1.3 during hypocalcemia to greater than 3 during hypercalcemia. These observations suggest that a fragment of parathyroid hormone, devoid of the aminoterminal portion of the molecule, originates in the parathyroid gland. The C:N ratios of peripheral plasma collected from three older conscious calves during induced alterations of plasma calcium concentration were similar to those observed in neonatal effluent plasma having an equivalent state of calcium concentration. It appears that both the secretion of carboxyl fragment(s) and the previously suggested postsecretory cleavage of parathyroid hormone by other organs may contribute to the carboxyl fragments found in the peripheral circulation. The similarity of the C:N ratios in peripheral and effluent plasma suggests that the secretion of fragments by the parathyroid gland contributes significantly to the concentration of carboxyl fragments in peripheral blood. This appears to be especially true during hypercalcemia, when the parathyroid gland secretes mostly fragments and only a small amount of intact hormone available for conversion to carboxyl fragment peripherally.