The expression of gastrin/cholecystokinin (CCK) peptides and their precursors was examined in 16 medullary carcinomas of the human thyroid. Measurements with libraries of sequence-specific radioimmunoassays before and after enzymatic cleavage of extracts and chromatographic fractions showed that the carcinomas contained 1·7 pmol carboxyamidated CCK/g tissue (median; range 0·6–21·8 pmol/g), 0·9 pmol glycine-extended precursor/g (median; range < 0·2–2·3 pmol/g) and 2·3 pmol further COOH-terminal-extended proCCK/g (median; range 0·9–6·2 pmol/g). Neither carboxyamidated gastrins nor any progastrins could be measured. Gel and reverse-phase chromatography revealed only small molecular forms, i.e. > 90% of the amidated immunoreactivity eluted like non-sulphated CCK-8 or CCK-7. The results show that human medullary thyroid carcinomas synthesize CCK peptides. The predominance of non-sulphated CCK is unusual. Taken together with earlier observations from dogs and pigs, our results raise the possibility that small non-sulphated CCK peptides modulate thyroid C-cell secretion in an autocrine manner.
Journal of Endocrinology (1990) 124, 501–506