Non-sulphated cholecystokinin in human medullary thyroid carcinomas.
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 less than 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. greater than 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.
Rehfeld
J F
JF
Department of Clinical Chemistry, Rigshospitalet, University of Copenhagen, Denmark.
Johnsen
A H
AH
Odum
L
L
Bardram
L
L
Schifter
S
S
Scopsi
L
L
D000595:Amino Acid Sequence; D002277:Carcinoma / Q000032:analysis*; D002766:Cholecystokinin / Q000032:analysis*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D005755:Gastrins / Q000032:analysis; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D011498:Protein Precursors / Q000032:analysis; D011863:Radioimmunoassay; D013964:Thyroid Neoplasms / Q000032:analysis*
D005755:Gastrins; D010446:Peptide Fragments; D011498:Protein Precursors; C042873:preprogastrin; C042082:preprocholecystokinin; D002766:Cholecystokinin