Regulation of lactase and sucrase-isomaltase gene expression in the duodenum during childhood.
BACKGROUND
In children, lactase and sucrase-isomaltase are essential intestinal glycohydrolases, and insufficiency of either enzyme causes diarrhea and malnutrition. Little is known about the regulation of lactase and sucrase-isomaltase expression in the duodenum during childhood. In this study, the mechanisms of regulation of duodenal expression of both enzymes were examined in a study population with ages ranging from 1 to 18 years.


METHODS
Duodenal biopsy specimens from 60 white children were used to analyze tissue morphology and to quantify lactase and sucrase-isomaltase mRNA and protein.


RESULTS
Among healthy subjects, high interindividual variability was noted in both mRNA and protein levels for lactase and sucrase-isomaltase. Lactase mRNA level per subject did not correlate with sucrase-isomaltase mRNA level and thus appeared independent. Both lactase and sucrase-isomaltase protein levels correlated significantly with their respective mRNA levels. For each enzyme, a significant inverse correlation was observed between the degree of villus atrophy and mRNA levels. Aging from 1 to 18 years did not result in significant changes in mRNA or protein levels of either enzyme. Immunostaining patterns within the duodenal epithelium for lactase differed from sucrase-isomaltase in adjacent sections, illustrating independent regulation at the cellular level.


CONCLUSIONS
In the duodenum of white children, lactase and sucrase-isomaltase seem primarily regulated at the transcriptional level. The expression of each enzyme in the intestinal epithelium is regulated by an independent mechanism. Lactase and sucrase-isomaltase exhibit stable mRNA and protein levels in healthy children as they grow to adulthood. Mucosal damage affected levels of both enzymes negatively.
Laboratory for Pediatric Gastroenterology and Nutrition, Academic Medical Center, University of Amsterdam, The Netherlands.
E H
EH
Van Beers
E H
EH
Rings
J A
JA
Taminiau
H S
HS
Heymans
A W
AW
Einerhand
J
J
Dekker
H A
HA
Büller
D000293:Adolescent; D000375:Aging; D000911:Antibodies, Monoclonal; D001284:Atrophy; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D004386:Duodenum / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007413:Intestinal Mucosa / Q000201:enzymology / Q000473:pathology; D043322:Lactase; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D013394:Sucrase-Isomaltase Complex / Q000235:genetics*; D001616:beta-Galactosidase / Q000235:genetics*
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D013394:Sucrase-Isomaltase Complex; D043322:Lactase; D001616:beta-Galactosidase