Abstract
Despite extensive study in both humans and nonhuman mammals the mechanisms which regulate intestinal lactase activity, particularly during development, are incompletely understood. Our previous studies of human adults are consistent with an important role of lactase-phlorizin hydrolase (LPH) mRNA abundance in determining the lactase persistence/nonpersistence phenotypes. Our intent in the present study was to determine the role of LPH mRNA in the regulation of lactase in children. We therefore studied duodenal mucosal biopsies from 39 children undergoing diagnostic upper endoscopy in whom significant small intestinal and nutritional disease was excluded. We found no relationship between the level of LPH mRNA and lactase enzymatic activity. Our observations suggest the importance of posttranscriptional mechanisms in lactase regulation in human children.
Similar content being viewed by others
Login or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- LPH:
-
lactase-phlorizin hydrolase
References
Welsh JD, Poley JR, Bhatia M, Stevenson DE 1978 Intestinal disaccharidase activities in relation to age, race, and mucosal damage. Gastroenterology 75: 847–855.
Lebenthal E, Antonowicz I, Schwachman H 1975 Correlation of lactase activity, lactose intolerance and milk consumption in different age groups. Am J Clin Nutr 28: 595–600.
Flatz G 1977 Genetics of lactose digestion in humans. Adv Hum Genet 16: 1–77.
Witte J, Lloyd M, Lorenzsonn V, Korsmo H, Olsen WA 1990 The biosynthetic basis of adult lactase deficiency. J Clin Invest 86: 1338–1342.
Sterchi E E, Mills PR, Fransen JAM, Hauri H-P, Lentze MJ, Naim HY, Ginsel L, Bond J 1990 Biogenesis of intestinal lactase-phlorizin hydrolase in adults with lactose intolerance. J Clin Invest 86: 1329–1337.
Lloyd M, Mevissen G, Fischer M, Olsen W, Goodspeed D, Genini M, Boll W, Semenza G, Mantei N 1992 Regulation of intestinal lactase in adult hypolactasia. J Clin Invest 89: 524–529.
Sebastio G, Villa M, Sartorio R, Guzzetta V, Poggi V, Auricchio S, Boll W, Mantei N, Semenza G 1989 Control of lactase in human adult-type hypolactasia and in weaning rabbits and rats. Am J Hum Genet 45: 489–497.
Escher JC, de Koning ND, van Engen CGJ, Arora S, Buller HA, Montgomery RK, Grand RJ 1992 Molecular basis of lactase levels in adult humans. J Clin Invest 89: 480–483.
Fajardo O, Naim HY, Lacey SW 1994 The polymorphic expression of lactase in adults is regulated at the messenger RNA level. Gastroenterology 106: 1233–1241.
Harvey CB, Wang Y, Hughes LA, Swallow DM, Thurrell WP, Sams VR, Barton R, Lanzon-Miller S, Sarner M 1995 Studies on the expression of intestinal lactase in different individuals. Gut 36: 28–33.
Wang Y, Harvey CB, Pratt WS, Sams VR, Sarner M, Rossi M, Auricchio S, Swallow DM 1995 The lactase persistence/nonpersistence polymorphism is controlled by a cis-acting element. Hum Mol Genet 4: 657–662.
Buller HA, Kothe MJC, Goldman DA, Grubman SA, Sassak MV, Matsudaira PT, Montgomery RK, Grand RJ 1990 Coordinate expression of lactase-phlorizin hydrolase mRNA and enzyme levels in rat intestine during development. J Biol Chem 265: 6978–6983.
Krasinski SD, Estrada G, Yeh KY, Yeh M, Traber PG, Rings EHHM, Buller HA, Verhave M, Montgomery RK, Grand RJ 1994 Transcriptional regulation of intestinal hydrolase biosynthesis during postnatal development in rats. Am J Physiol 267: G584–G594.
Keller P, Zwicker E, Mantei N, Semenza G 1992 The levels of lactase and of sucrase-isomaltase along the rabbit small intestine are regulated both at the mRNA level and post-translationally. FEBS Lett 313: 265–269.
Troelsen JT, Mehlum A, Olsen J, Spodsberg N, Hansen GH, Prydz H, Noren O, Sjostrom H 1994 1 kb of the lactase-phlorizin hydrolase promoter directs post-weaning decline and small intestinal-specific expression in transgenic mice. FEBS Lett 342: 291–296.
Nudell DM, Santiago NA, Zhu J-S, Cohen ML, Majuk Z, Gray GM 1993 Intestinal lactase: maturational excess expression of mRNA over enzyme protein. Am J Physiol 265: G1108–G1115.
Freund J-N, Duluc I, Raul F 1991 Lactase expression is controlled differently in the jejunum and ileum during development in rats. Gastroenterology 100: 388–394.
Duluc I, Jost B, Freund J-N 1993 Multiple levels of control of the stage- and region-specific expression of rat intestinal lactase. J Cell Biol 123: 1577–1586.
Nsi-Emvo E, Launay JF, Raul F 1987 Is adult-type hypolactasia in the intestine of mammals related to changes in the intracellular processing of lactase? Cell Mol Biol 33: 335–344.
Quan R, Santiago NA, Tsuboi KK, Gray GM 1990 Intestinal lactase. Shift in intracellular processing to altered, inactive species in the adult rat. J Biol Chem 265: 15882–15888.
Castillo RO, Reisenauer AM, Kwong LK, Tsuboi KK, Quan R, Gray GM 1990 Intestinal lactase in the neonatal rat. Maturational changes in intracellular processing and brush-border degradation. J Biol Chem 265: 15889–15893.
Kwong WKL, Seetharam B, Alpers DH 1978 Effect of exocrine pancreatic insufficiency on small intestine in mouse. Gastroenterology 74: 1277–1282.
Dahlqvist A 1968 Assay of intestinal disaccharidases. Anal Biochem 22: 99–107.
Kroczek RA, Siebert E 1990 Optimization of Northern analysis by vacuum blotting, RNA-transfer visualization, and ultraviolet fixation. Anal Biochem 184: 90–95.
Mantei N, Villa M, Enzler T, Wacker H, Boll W, James P, Hunziker W, Semenza G 1988 Complete primary structure of human and rabbit lactase-phlorizin hydrolase: implications for biosynthesis, membrane anchoring and evolution of the enzyme.. EMBO J 7: 2705–2713.
Gunning P, Ponte P, Okayama H, Engel J, Blau H, Kedes L 1983 Isolation and characterization of full-length cDNA clones for human-, -, and G-actin mRNAs: skeletal but not cytoplasmic actins have an amino-terminal cysteine that is subsequently removed. Mol Cell Biol 3: 787–795.
Auricchio S, Rubino A, Semenza G, Landolt M, Prader A 1963 Isolated intestinal lactase deficiency in the adult. Lancet 2: 324–326.
Dahlqvist A, Hammond J, Crane RK, Dunphy JV, Littman A 1963 Intestinal lactase deficiency and lactose intolerance in adults: preliminary report. Gastroenterology 45: 488–491.
Cuatrecasas P, Lockwood DH, Caldwell JF 1965 Lactase deficiency in the adult. A common occurrence. Lancet 2: 14–18.
Maiuri L, Rossi M, Raia V, D'Auria S, Swallow D, Quaroni A, Auricchio S 1992 Patchy expression of lactase protein in adult and rat intestine. Gastroenterology 103: 1739–1746.
Rings EHHM, Krasinski SD, Van Beers EH, Moorman AFM, Dekker J, Montgomery RK, Grand RJ, Buller HA 1994 Restriction of lactase gene expression along the proximal-to-distal axis of rat small intestine occurs during postnatal development. Gastroenterology 106: 1223–1232.
Arvanitakis C, Olsen WA 1974 Intestinal mucosal disaccharidases in chronic pancreatitis. Am J Dig Dis 19: 417–421.
Robberecht P, Deschodt-Lanckman M, Camus J, Bruylands J, Christophe J 1971 Rat pancreatic hydrolases from birth to weaning and dietary adaptation after weaning. Am J Physiol 221: 376–381.
Maiuri L, Raia V, Potter J, Swallow D, Ho MW, Giocca R, Finzi G, Cornaggia M, Capella C, Quaroni A, Auricchio S 1991 Mosaic pattern of lactase expression by villous enterocytes in human adult-type hypolactasia. Gastroenterology 100: 359–369.
Lorenzsonn V, Lloyd M, Olsen WA 1993 Immunocytochemical heterogeneity of lactase-phlorizin hydrolase in adult lactase deficiency. Gastroenterology 105: 51–59.
Maiuri L, Rossi M, Raia V, Garipoli V, Hughes LA, Swallow D, Noren O, Sjostrom H, Auricchio S 1994 Mosaic regulation of lactase in human adult-type hypolactasia. Gastroenterology 107: 54–60.
Author information
Authors and Affiliations
Additional information
Supported by Veterans Administration Research Funds and Grant R-29-DK 45785(to M.L.) from the National Institute of Diabetes and Digestive and Kidney Diseases.
Rights and permissions
About this article
Cite this article
Olsen, W., Li, B., Lloyd, M. et al. Heterogeneity of Intestinal Lactase Activity in Children: Relationship to Lactase-Phlorizin Hydrolase Messenger RNA Abundance. Pediatr Res 39, 877–881 (1996). https://doi.org/10.1203/00006450-199605000-00023
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1203/00006450-199605000-00023
