Epidermal growth factor (EGF) accelerates the maturation of fetal mouse intestinal mucosa in utero

Abstract

Summary. Pregnant Swiss ICR mice were injected i.p. with 0.5 ~tg of epidermal growth factor (EGF) per g b.wt at 15,16 and 17 days of gestation and fetuses were removed at 18 days of gestation. EGF treatment had no effect on the weight of the fetuses and on the length of the small intestine. No modification of the protein and DNA contents was noted. However brush border alkaline phosphatase and trehalase activities were significantly increased as well as endoplasmic reticulum membrane-bound glucose-6-phosphatase.Epidermal growth factor (EGF) is a small polypeptide mitogen that has been isolated from the male mouse submaxillary gland 2 and from human urine 3. The presence of EGF in human Brunner's gland, shown by Elder et al. 4, suggests that EGF may have a role in mucosal growth and control of gastrointestinal secretion. In the adult male mouse Scheving et al. 5'6 have demonstrated that EGF rapidly stimulates DNA synthesis in some regions of the digestive tract. In the newborn mouse EGF stimulates ornithine decarboxylase activity in the stomach and duodenum 7 and accelerates the maturation of the intestinal mucosa 8. Using an organ culture method of fetal mouse small intestine, we have observed that EGF induces the differentiation of the rough endoplasmic reticulum in absorptive cells after 72 h of culture 9. The aim of this work was to determine the effect of EGF on the fetal mouse small intestine in utero by measuring the protein and DNA contents as well as enzymatic activities of the brush border and endoplasmic reticulum. Results were comparable with both products. Fetuses were removed at 18 days of gestation. The entire small intestine of the fetuses was removed, measured and cut into 3 equal parts. For each assay, the intestinal thirds of 5 fetuses were pooled, weighed and homogenized in 49 vol. of ice-cold red• water in an Omnimixer during 2 min at full speed. The homogenates were used immediately for enzymatic determinations. Protein was measured by the method of Lowry et al. l~ with bovine serum albumine as standard and DNA content was determined by the method of Burton" as modified by Giles Results and discussion. The effects of daily injections of EGF for 3 days beginning at 15 days of gestation have been studied in the small intestine of fetuses at 18 days of gestation. As shown in table 1 the weight of the EGFtreated fetuses, the length of their small intestine and the weight of the different intestinal segments are comparable to that of the controls. Furthermore no modification of the protein and DNA contents is noted along the small intestine. The development of some brush border membrane hydrolytic activities has been investigated. Significant increases of alkaline phosphatase and trehalase activities are recorded along the entire length of the small intestine following EGF treatment (table 2), except for trehalase activity in the distal thirds where the increase is nonsignificant. It is interesting to note that even though alkaline phosphatase and trehalase activities increase following EGF treatm...

Urogastrone and Lactose Concentrations in Precolostrum, Colostrum, and Milk

“…The gradual decrease in URO concentration in the prepartum period in the normal secretor (KD) was matched by a gradual increase in milk lactose concentration; however, the URO levels in precolostrum reported for this individual were in general lower than those measured in the other three hypersecrean increase in DNA content of the small intestine' was reported (17,34), when neonates were fed colostrum as an alternative to water or an isocaloric artificial formula. Furthermore, there is a large amount of evidence to show that EGF/URO exerts atrophic effect on the mucosa of the stomach and small intestine of both adult and neonatal animals (2,5,9,10,22,26,30). Although URO has also been localized in Brunner's gland in the adult human duodenum (18), its presence in the newborn has not been investigated.…”

Is Dietary Epidermal Growth Factor Absorbed by Premature Human Infants?

“…A role for EGF in early human development is suggested by experiments with mice, rats, rabbits, and lambs in which EGF given to fetal animals accelerated developmental pro cesses in lung [1,2] and gastrointestinal tract [5,[18][19][20]. It seems possible that the poorly developing infant might benefit most from the trophic actions of EGF, because the rat intestine is more responsive to EGF follow ing gut resection [21], starvation [19], or atrophy associated with removal of enteral nutrition [20] while the onset of respiratory distress syndrome in the prematurely deliv ered lamb can be prevented by injection of EGF into the fetus [2], Also higher concen trations of EGF occur in milk from mothers of premature infants [22],…”

Effect of Necrotizing Enterocolitis on Urinary Epidermal Growth Factor Levels

“…Feedings were initiated by 1 week (Table 2) in 27 infants and no significant changes were noted in EGF/Cr levels during this period. Ten infants received no oral nu¬ trition for longer than 1 week of life with sepsis as their primary diagnosis. Their EGF/Cr values at 1 week were significantly decreased from day 1 (P<.05).…”