Fetal abnormalities in cystic fibrosis suggest a deficiency in proteolysis of cholecystokinin.

Ultrastructural and microvillous enzyme (MVE) histochemical studies of fetuses with cystic fibrosis (CF) and trisomies 13 and 18 identified features in CF which differed from the abnormalities in trisomies 13 and 18. The principal abnormalities in CF were in the tight (occluding) junctions and intracellular organelles, particularly the golgi and mitochondria, of the epithelial cells of the pancreas, respiratory system, intestine, and gallbladder. Abnormalities of amniotic fluid MVE levels in CF and trisomy 13 occur because of disruption of the pathways by which the MVE reach the amniotic fluid. Trisomy 18 shows hypoplasia and deficiency of epithelial cell microvilli. It is postulated that the basic defect in CF is due to the deficiency of an enzyme that cleaves the Arg-Asp peptide bond in cholecystokinin to produce the active octapeptide CCK-8, which normally stimulates exocrine secretion, especially in pancreas, gallbladder, and intestine, and potentiates the action of other gastrointestinal hormones.