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

Abstract

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.

Development of Glucocorticoid-Responsiveness in Mouse Intestine

“…Likewise, although investigators have found significant maturation of intestinal motility (8) and permeability (9) in premature infants whose mothers received prenatal glucocorticoid, another study reported no effect on lactase maturation (10). The latter in vivo observation is in contrast to several studies that have shown elevation of lactase activity in response to glucocorticoid treatment in explant cultures of human fetal intestine (11)(12)(13). We hypothesize that such seemingly disparate results may be explained by differences in dosages and timing of corticosteroid treatment.…”

Expression of Human Intestinal mRNA Transcripts during Development: Analysis by a Semiquantitative RNA Polymerase Chain Reaction Method

“…Our results on the expression of lactase mRNA in the small intestine correlate reasonably well with those reported for the distribution of the enzyme activity and the presence of the lactase protein. Lactase activity has, for example, been shown to be very low before the 24th wk of gestation (5,7,8,18), and a low level of lactase mRNA was obsenred in the recent study by Villa et al (18). It is of interest that very low but detectable levels of lactase mRNA were also found in fetal colon, because conflicting results have been obtained for the expression of lactase protein in fetal colon.…”

“…This is also the case for the carbonic anhydrase 1 transcript, although this transcript is not expressed in the small intestine. Thus, each of these genes shows different developmental and cell-specific reg- RT mix, reverse transcription mixture the small intestine (12, [16][17][18][19][20][21][22], information is limited, particularly in humans, concerning their relative expression at different stages of development and in different parts of the intestine. It is hard to compare the results obtained in different studies on different samples by different methods.…”

The levels of lactase and of sucrase‐isomaltase along the rabbit small intestine are regulated both at the mRNA level and post‐translationally

“…We conclude, therefore, that both the mRNA levels and a post-translational mechanism determine the steady-state levels of lactase along the small intestine of young and adult rabbits. We have already suggested two regulatory mechanisms to operate in the biosynthesis of LPH in fetal small intestine [21].…”

“…Total lactase activity, a¢id-fl-galactosidase activity, and brush border lactase activity were determined as described by Villa et al [21]. Suerase activity was measured at 37°C in 33 mM Na-malgale buffer, pH 6.0, using 33 mM sucrose as substmte.…”