Discrepancy between the intestinal lactase enzymatic activity and mRNA accumulation in sucklings and adults Effect of starvation and thyroxine treatment

Freund, Jean–Noël; Duluc, Isabelle; Raul, Françis

doi:10.1016/0014-5793(89)80427-2

Cited by 46 publications

(25 citation statements)

References 15 publications

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“…remains a possibility. Recently, it has been reported that the thyroxine-induced precocious decline in lactase activity in suckling rats was not correlated with any modification of the mRNA levels, and the authors suggested a post-transcriptional regulation of Iactase expression by thyroxine in this animal model [27]. This modulation of lactase expression contrasts with that of another wellknown brush border enzyme, namely sucrase-isomaltase.…”

Section: Discussionmentioning

confidence: 86%

The expression of lactase enzymatic activity and mRNA in human fetal jejunum Effect of organ culture and of treatment with hydrocortisone

et al. 1992

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Very sensitive procedures were developed for the parullel determination of intestinal lactase (LPH) activity and the cognate mRNA. Between 14 and 20 weeks of gestation, lactase activity is low and varies only slightly; at 37 weeks, a relatively high level of activity is observed. The amounts of LPH mRNA correlates with the enzymatic activity (r = 0.64). Culture of fetal jejunal explants for 5 days induces by itself a 2.fold increase in LPI-I mRNA, without any significant change in lactase enzymatic activity. This increase may reflect the loss ofa negative transcriptional regulation opcldtive in vivo, and suggests an additional post-transcriptional regulatory componenl, The addition of hydrocortisone (50 n&/ml) during culture induces a doubling of lactuse activity without variation in LHP mRNA, indicating a post-transcriptional modulation by hydrocortisone, The intestinal lysosomal ucid &guluctosidase activity wus shown to bc unaffected by hydrocortisone treatment. This observation clearly illustrates that the two intestinal P~galactosidascs are regulated differently. Our results suggests a complex developmental regulation of human intestinal lactase and [hut the perinatal increase in lactase activity could be modulated at a post-transcriptional level by hydrocortisone.

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Section: Discussionmentioning

confidence: 86%

The expression of lactase enzymatic activity and mRNA in human fetal jejunum Effect of organ culture and of treatment with hydrocortisone

et al. 1992

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“…LPH is unique among intestinal hydrolases in its precipitous decline in activity coincident with the onset ofweaning in most mammalian species. The molecular mechanisms responsible for this phenomena have been the focus of recent studies, but controversy persists as to whether the primary control of LPH gene expression in the intestine occurs at the level of transcription or during subsequent cellular events (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

Regulation of intestinal lactase in adult hypolactasia.

Lloyd

Mevissen²,

Fischer³

et al. 1992

J. Clin. Invest.

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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. (J. Clin. Invest. 1992.

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“…These reports support a transcriptional mechanism for regulating the lactase maturational decline. However, a lack of correlation between the decline in lactase mRNA and enzyme expression also has been described in rats (5,7,8), rabbits (9), pigs (10), and humans (8), suggesting that post-transcriptional mechanisms may also play a role in the maturational activity decline.…”

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confidence: 99%

Regulation of Intestine-specific Spatiotemporal Expression by the Rat Lactase Promoter

Lee

Wang

Lin

et al. 2002

Journal of Biological Chemistry

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Lactase gene transcription is spatially restricted to the proximal and middle small intestine of the developing mouse. To identify regions of the lactase gene involved in mediating the spatiotemporal expression pattern, transgenic mice harboring 0.8-, 1.3-, and 2.0-kb fragments of the 5-flanking region cloned upstream of a firefly-luciferase reporter were generated. Transgene expression was assessed noninvasively in living mice using a sensitive low light imaging system. Two independent, 1.3-and 2.0-kb, lactase promoter-reporter transgenic lines expressed appropriate high levels of luciferase activity in the small intestine (300 -3,000 relative light units/g) with maximal expression in the middle segments. Post-weaned 30-day transgenic offspring also demonstrated an appropriate 4-fold maturational decline in luciferase expression in the small intestine. The pattern of the 2.0-kb promoter transgene mRNA abundance most closely mimicked that of the endogenous lactase gene with respect to spatiotemporal restriction. In contrast, a 0.8-kb promoter-reporter construct expressed low level luciferase activity (<25 relative light units/g) in multiple organs and throughout the gastrointestinal tract in transgenic mice. Thus, a distinct 5-region of the lactase promoter directs intestine-specific expression in the small intestine of transgenic mice, and regulatory sequences have been localized to a 1.2-kb region upstream of the lactase transcription start site. In addition, we have demonstrated that in vivo bioluminescence imaging can be utilized for assessment of intestinal expression patterns of a luciferase reporter gene driven by lactase promoter regions in transgenic mice.Intestinal lactase-phlorizin hydrolase (LPH, 1 lactase) is the absorptive enterocyte membrane glycoprotein essential for digestive hydrolysis of lactose in milk. Lactase is present predominantly along the brush-border membrane of differentiated enterocytes lining the villi of the small intestine. Expression of the lactase gene is spatially restricted along the longitudinal axis of the gut (1). The lactase gene is expressed maximally in the proximal and middle small intestine and declines significantly in the distal segments of the intestine. Lactase gene expression is also temporally restricted in the gut during intestinal maturation. Enzyme activity is maximal in the small intestine of pre-weaned mammals and declines markedly during maturation. The maturational decline in lactase activity contrasts with a maturational increase in enzymatic activity of other intestinal hydrolases essential for digestion of solid foods (for comprehensive review see Ref. 2).Although the mechanisms regulating the spatial and temporal restriction of lactase gene expression have not been fully defined, lactase spatiotemporal restriction is largely regulated at the level of gene transcription. This is suggested by colocalization of lactase protein along the longitudinal axis of the gut and lactase mRNA transcripts detected by Northern blot and in situ hybridization (1). With...

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Discrepancy between the intestinal lactase enzymatic activity and mRNA accumulation in sucklings and adults Effect of starvation and thyroxine treatment

Cited by 46 publications

References 15 publications

The expression of lactase enzymatic activity and mRNA in human fetal jejunum Effect of organ culture and of treatment with hydrocortisone

The expression of lactase enzymatic activity and mRNA in human fetal jejunum Effect of organ culture and of treatment with hydrocortisone

Regulation of intestinal lactase in adult hypolactasia.

Regulation of Intestine-specific Spatiotemporal Expression by the Rat Lactase Promoter

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