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. 1992 Feb;89(2):524–529. doi: 10.1172/JCI115616

Regulation of intestinal lactase in adult hypolactasia.

M Lloyd 1, G Mevissen 1, M Fischer 1, W Olsen 1, D Goodspeed 1, M Genini 1, W Boll 1, G Semenza 1, N Mantei 1
PMCID: PMC442883  PMID: 1737843

Abstract

Relative deficiency of intestinal lactase activity during adulthood, adult hypolactasia, is a common condition worldwide. We studied the regulation of lactase-phlorizin hydrolase in normal and adult hypolactasic subjects by correlating transcript abundance in intestinal biopsies with relative synthetic rates for the protein in cultured intestinal explants. After metabolic labelling studies in six subjects, precursor lactase-phlorizin hydrolase was identified in amounts directly proportional to the enzyme-specific activity suggesting that levels of intestinal lactase are regulated by synthetic rate. Total intestinal RNA was extracted from biopsies of these subjects and three hypolactasic adults who had participated in previous biosynthesis studies. Transcript levels were markedly reduced in deficient subjects who demonstrated diminished lactase-phlorizin hydrolase synthesis. The sequence of 1 kb of 5'-flanking region of the lactase-phlorizin hydrolase gene was determined in two hypolactasic subjects and two controls. No sequence variability was identified to account for differences in mRNA levels or biosynthetic rates between the two groups. A single hypolactasic subject previously characterized as demonstrating delayed posttranslational processing, showed message levels intermediate between other deficients and controls. These results suggest that in the majority of our subjects, pretranslational mechanisms account for the predominate regulatory control of lactase-phlorizin hydrolase expression in the proximal intestine.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Boll W., Wagner P., Mantei N. Structure of the chromosomal gene and cDNAs coding for lactase-phlorizin hydrolase in humans with adult-type hypolactasia or persistence of lactase. Am J Hum Genet. 1991 May;48(5):889–902. [PMC free article] [PubMed] [Google Scholar]
  2. Burke T., Lloyd M., Lorenzsonn V., Olsen W. Synthesis and intracellular processing of aminooligopeptidase by human intestine. Gastroenterology. 1988 Jun;94(6):1426–1431. doi: 10.1016/0016-5085(88)90682-8. [DOI] [PubMed] [Google Scholar]
  3. Büller H. A., Kothe M. J., Goldman D. A., Grubman S. A., Sasak W. V., Matsudaira P. T., Montgomery R. K., Grand R. J. Coordinate expression of lactase-phlorizin hydrolase mRNA and enzyme levels in rat intestine during development. J Biol Chem. 1990 Apr 25;265(12):6978–6983. [PubMed] [Google Scholar]
  4. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  5. Dahlqvist A. Assay of intestinal disaccharidases. Anal Biochem. 1968 Jan;22(1):99–107. doi: 10.1016/0003-2697(68)90263-7. [DOI] [PubMed] [Google Scholar]
  6. Freund J. N., Duluc I., Raul F. Discrepancy between the intestinal lactase enzymatic activity and mRNA accumulation in sucklings and adults. Effect of starvation and thyroxine treatment. FEBS Lett. 1989 May 8;248(1-2):39–42. doi: 10.1016/0014-5793(89)80427-2. [DOI] [PubMed] [Google Scholar]
  7. Freund J. N., Duluc I., Raul F. Lactase expression is controlled differently in the jejunum and ileum during development in rats. Gastroenterology. 1991 Feb;100(2):388–394. doi: 10.1016/0016-5085(91)90207-2. [DOI] [PubMed] [Google Scholar]
  8. Grosveld F., van Assendelft G. B., Greaves D. R., Kollias G. Position-independent, high-level expression of the human beta-globin gene in transgenic mice. Cell. 1987 Dec 24;51(6):975–985. doi: 10.1016/0092-8674(87)90584-8. [DOI] [PubMed] [Google Scholar]
  9. Gunning P., Ponte P., Okayama H., Engel J., Blau H., Kedes L. Isolation and characterization of full-length cDNA clones for human alpha-, beta-, and gamma-actin mRNAs: skeletal but not cytoplasmic actins have an amino-terminal cysteine that is subsequently removed. Mol Cell Biol. 1983 May;3(5):787–795. doi: 10.1128/mcb.3.5.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Herrmann B. G., Frischauf A. M. Isolation of genomic DNA. Methods Enzymol. 1987;152:180–183. doi: 10.1016/0076-6879(87)52018-3. [DOI] [PubMed] [Google Scholar]
  11. Kreitman M., Landweber L. F. A strategy for producing single-stranded DNA in the polymerase chain reaction. A direct method for genomic sequencing. Gene Anal Tech. 1989 Jul-Aug;6(4):84–88. doi: 10.1016/0735-0651(89)90021-6. [DOI] [PubMed] [Google Scholar]
  12. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  13. Lloyd M. L., Olsen W. A. A study of the molecular pathology of sucrase-isomaltase deficiency. A defect in the intracellular processing of the enzyme. N Engl J Med. 1987 Feb 19;316(8):438–442. doi: 10.1056/NEJM198702193160804. [DOI] [PubMed] [Google Scholar]
  14. Maiuri L., Raia V., Potter J., Swallow D., Ho M. W., Fiocca R., Finzi G., Cornaggia M., Capella C., Quaroni A. Mosaic pattern of lactase expression by villous enterocytes in human adult-type hypolactasia. Gastroenterology. 1991 Feb;100(2):359–369. doi: 10.1016/0016-5085(91)90203-w. [DOI] [PubMed] [Google Scholar]
  15. Mantei N., Villa M., Enzler T., Wacker H., Boll W., James P., Hunziker W., Semenza G. Complete primary structure of human and rabbit lactase-phlorizin hydrolase: implications for biosynthesis, membrane anchoring and evolution of the enzyme. EMBO J. 1988 Sep;7(9):2705–2713. doi: 10.1002/j.1460-2075.1988.tb03124.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Sebastio G., Villa M., Sartorio R., Guzzetta V., Poggi V., Auricchio S., Boll W., Mantei N., Semenza G. Control of lactase in human adult-type hypolactasia and in weaning rabbits and rats. Am J Hum Genet. 1989 Oct;45(4):489–497. [PMC free article] [PubMed] [Google Scholar]
  18. Sterchi E. E., Mills P. R., Fransen J. A., Hauri H. P., Lentze M. J., Naim H. Y., Ginsel L., Bond J. Biogenesis of intestinal lactase-phlorizin hydrolase in adults with lactose intolerance. Evidence for reduced biosynthesis and slowed-down maturation in enterocytes. J Clin Invest. 1990 Oct;86(4):1329–1337. doi: 10.1172/JCI114842. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Welsh J. D., Poley J. R., Bhatia M., Stevenson D. E. Intestinal disaccharidase activities in relation to age, race, and mucosal damage. Gastroenterology. 1978 Nov;75(5):847–855. [PubMed] [Google Scholar]
  20. Witte J., Lloyd M., Lorenzsonn V., Korsmo H., Olsen W. The biosynthetic basis of adult lactase deficiency. J Clin Invest. 1990 Oct;86(4):1338–1342. doi: 10.1172/JCI114843. [DOI] [PMC free article] [PubMed] [Google Scholar]

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