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.
Van Beers
E H
EH
Laboratory for Pediatric Gastroenterology and Nutrition, Academic Medical Center, University of Amsterdam, The Netherlands.
Rings
E H
EH
Taminiau
J A
JA
Heymans
H S
HS
Einerhand
A W
AW
Dekker
J
J
Büller
H A
HA
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