1-34 Human parathyroid hormone radioimmunoassay: Properties of antiserum against synthetic 1-34 human parathyroid hormone and its clinical application.

Abstract

Antibody against synthetic 1-34 humanPTH synthesized by Niall et al.(1974), was developed in rabbits. Synthetic 1-34 hPTH was found to be a good immunogen for rabbit. The relative importance of various structural parts of 1-34 hPTH molecule with regard to immunological specificity was determined by reference to inhibition of specific binding of ¹²⁵I-1-34 hPTH to the antibody by analogues of 1-34 hPTH (NLeu⁸-NLeu¹⁸ 1-34 hPTH, NLeu⁸-NLeu¹⁸-Tyr³⁴hPTH) and by 1-34 bPTH. The immunological recognition site in 1-34 hPTH molecule was found to be located around the 8 to 18 amino acid sequence, because the binding affinity to the antibody of this analogue (NLeu⁸-NLeu¹⁸1-34 hPTH) was less than that of the native hormone in the antibody. Furthermore, other immunological recognition sites were located in the C- and N-terminal regions of this molecule, as reported by Segre et al.(1976) and Visser et al.(1979). This antiserum could measure only 1-34 hPTH molecule in serum, since it did not crossreact with partially purified 1-84 hPTH. In order to evaluate the advantage of 1-34 hPTH radio-immunoassay (RIA) in the diagnosis of parathyroid dysfunction, serum PTH levels in various diseases were measured by both 1-34 hPTH RIA and 1-84 PTH RIA and the values obtained by these assays were compared. There was a good correlation between the values obtained by 1-34 hPTH RIA and those by 1-84 PTH RIA. However, in patients with chronic renal failure, the incidence of cases with high serum PTH level was 90% when measured by 1-84 PTH RIA while it was 39% when measured by 1-34 hPTH RIA. Serum PTH levels in primary hyperparathyroidism were abnormally high and those in hypoparathyroidism were low in both assays. Some patients with senile osteoporosis had a high serum PTH level. The incidences of cases with a high serum PTH level in this disease were equal in both assays. In conclusion, these two site specific RIAs (1-34 PTH RIA and 1-84 PTH RIA) were useful in the evaluation of PTH secretion and / or metabolism.