MOLECULAR WEIGHT FORMS OF IMMUNOREACTIVE CALCITONIN IN A PATIENT WITH MEDULLARY CARCINOMA OF THE THYROID: DYNAMIC STUDIES WITH CALCIUM, PENTAGASTRIN AND SOMATOSTATIN

Abstract

The characteristics of circulating immunoreactive human calcitonin (IR-hCT) were examined by studying its different MW forms under various secretory conditions in a patient with medullary carcinoma of the thyroid. Plasma IR-hCT (318 mg/l basal) increased 9 and 12 times, respectively, after Ca (0.3 mg/kg per min over 10 min i.v.) and pentagastrin (3.2 .mu.g i.v.) administration. Somatostatin infusion (500 .mu.g/h) caused a 41% decrease in plasma IR-hCT and markedly diminished the responses to both pentagastrin and Ca. Sephadex G50 chromatography separated different IR-hCT forms: hCT itself predominated after stimulation with either Ca or pentagastrin (52% and 62%, respectively), while it was reduced in the basal state (33%) and following somatostatin (11%); reciprocal changes were observed for the higher MW forms. Under denaturing conditions, with or without reducing agent, total plasma IR-hCT was resolved into 1 major peak co-eluting with 125I-hCT. Thus, the hCT monomer appears to be the major secretory product of the medullary carcinoma of the thyroid. The predominance of higher MW forms in the basal state reflects their slower plasma disappearance rate. These high MW forms are mainly the result of aggregation or non-covalent protein binding of the hCT monomer.