Molecular Heterogeneity and Biological Activity of Immunoreactive Somatostatin in Medullary Carcinoma of the Thyroid*

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Abstract
Two cases of somatostatin (SRIF)-producing medullary carcinoma of the thyroid are presented. The plasma levels of SRIF and calcitonin changed in accordance with the clinical course before and after resection of the tumor. On chromatographic analysis of tumor extracts derived from primary and metastatic tumors of medullary thyroid carcinoma, at least two components of immunoreactive SRIF (IR-SRIF) of large molecular size were found, besides a component corresponding to the tetradecapeptide (SRIF 14); one of these seemed to have almost the same molecular weight as the octacosapeptide (SRIF 28). Most of the IR-SRIF in one patient’s plasma was eluted in the same position as tetradecapeptide SRIF. The biological activity of SRIF recovered from the tumor extract was assessed by measuring activity for inhibiting GH release using dispersed rat anterior pituitary cells. GH release from the cells into the incubation medium tended to decrease at a concentration of 1 × 10−9 M IR-SRIF derived from the tumor (3000 ± 482 ng/105 cells-3 h) compared with the control value (4288 ± 567 ng/105 cells · 3 h). A significant decrease was observed at concentrations of 1 × 10−8 M (1880 ± 403 ng/105 cells-3 h) and 5 × 10−8 M (938 ± 262 ng/105 cells-3 h). Responses to equivalent amounts of synthetic SRIF 14 were similar. This suggests that IR-SRIF in the tumor has almost the same biological activity as synthetic tetradecapeptide SRIF.