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. 1989 Mar;30(3):327–332. doi: 10.1136/gut.30.3.327

Minimal hydrolysis of epidermal growth factor by gastric fluid of preterm infants.

J R Britton 1, C George-Nascimento 1, J N Udall 1, O Koldovský 1
PMCID: PMC1378454  PMID: 2785073

Abstract

Epidermal growth factor (EGF), present in high concentrations in milk, may play a role in growth of the gastrointestinal tract. Resistance to proteolytic degradation in the stomach is necessary if ingested EGF is to function within the gastrointestinal tract. Although EGF stability to low pH and proteases predicts gastric survival, the extent of digestion in the stomach remains to be defined. Consequently, we measured gastric degradation of 125I-human recombinant EGF in preterm infants with an in vitro method in which EGF was incubated at 37 degrees C with stomach fluid at pH 1.8, 3.2, and 5.8 followed by analysis of degradation products. As maximal acid proteolytic activity is present one hour after feeding in preterm infants, fluid was obtained at that time from 18 infants with a mean gestational age at birth of 30.4 (3.0) (SD) weeks and a postnatal age of 26.3 (12.7) days at sampling. Incubations for up to 60 minutes revealed minimal loss of trichloroacetic acid precipitable radioactivity, in contrast to the substantial hydrolysis of iodinated casein which occurred under the same conditions. Chromatography of reaction mixtures on Sephadex G-25 showed a single major peak of radioactivity which coeluted with EGF. Epidermal growth factor also retained greater than 75% of its ability to bind to anti-EGF affinity columns and placental membrane receptors after incubation with gastric fluid. These data support the concept of substantial gastric survival of ingested EGF in a potentially biologically active form in preterm infants.

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Selected References

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  1. Arsenault P., Ménard D. Stimulatory effects of epidermal growth factor on deoxyribonucleic acid synthesis in the gastrointestinal tract of the suckling mouse. Comp Biochem Physiol B. 1987;86(1):123–127. doi: 10.1016/0305-0491(87)90186-6. [DOI] [PubMed] [Google Scholar]
  2. Avery G. B., Randolph J. G., Weaver T. Gastric acidity in the first day of life. Pediatrics. 1966 Jun;37(6):1005–1007. [PubMed] [Google Scholar]
  3. Beardmore J. M., Lewis-Jones D. I., Richards R. C. Urogastrone and lactose concentrations in precolostrum, colostrum, and milk. Pediatr Res. 1983 Oct;17(10):825–828. doi: 10.1203/00006450-198310000-00012. [DOI] [PubMed] [Google Scholar]
  4. Berseth C. L. Breast-milk-enhanced intestinal and somatic growth in neonatal rats. Biol Neonate. 1987;51(1):53–59. doi: 10.1159/000242631. [DOI] [PubMed] [Google Scholar]
  5. Berseth C. L., Lichtenberger L. M., Morriss F. H., Jr Comparison of the gastrointestinal growth- promoting effects of rat colostrum and mature milk in newborn rats in vivo. Am J Clin Nutr. 1983 Jan;37(1):52–60. doi: 10.1093/ajcn/37.1.52. [DOI] [PubMed] [Google Scholar]
  6. Bower J. M., Camble R., Gregory H., Gerring E. L., Willshire I. R. The inhibition of gastric acid secretion by epidermal growth factor. Experientia. 1975 Jul 15;31(7):825–826. doi: 10.1007/BF01938488. [DOI] [PubMed] [Google Scholar]
  7. Britton J. R., Koldovský O. Development of luminal protein digestion in suckling and weanling rats. Biol Neonate. 1988;53(1):39–46. doi: 10.1159/000242760. [DOI] [PubMed] [Google Scholar]
  8. Brown K. D., Blakeley D. M. Cell growth-promoting activity in mammary secretions of the goat, cow and sheep. Br Vet J. 1983 Jan-Feb;139(1):68–78. doi: 10.1016/s0007-1935(17)30594-8. [DOI] [PubMed] [Google Scholar]
  9. Byyny R. L., Orth D. N., Cohen S. Radioimmunoassay of epidermal growth factor. Endocrinology. 1972 May;90(5):1261–1266. doi: 10.1210/endo-90-5-1261. [DOI] [PubMed] [Google Scholar]
  10. Carpenter G., Cohen S. Epidermal growth factor. Annu Rev Biochem. 1979;48:193–216. doi: 10.1146/annurev.bi.48.070179.001205. [DOI] [PubMed] [Google Scholar]
  11. Carpenter G. Epidermal growth factor is a major growth-promoting agent in human milk. Science. 1980 Oct 10;210(4466):198–199. doi: 10.1126/science.6968093. [DOI] [PubMed] [Google Scholar]
  12. Cohen S., Carpenter G., Lembach K. J. Interaction of epidermal growth factor (EGF) with cultured fibroblasts. Adv Metab Disord. 1975;8:265–284. doi: 10.1016/b978-0-12-027308-9.50024-x. [DOI] [PubMed] [Google Scholar]
  13. Defize J., Meuwissen S. G. Pepsinogens: an update of biochemical, physiological, and clinical aspects. J Pediatr Gastroenterol Nutr. 1987 Jul-Aug;6(4):493–508. [PubMed] [Google Scholar]
  14. Elder J. B., Ganguli P. C., Gillespie I. E., Gerring E. L., Gregory H. Effect of urogastrone on gastric secretion and plasma gastrin levels in normal subjects. Gut. 1975 Nov;16(11):887–893. doi: 10.1136/gut.16.11.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Elder J. B., Williams G., Lacey E., Gregory H. Cellular localisation of human urogastrone/epidermal growth factor. Nature. 1978 Feb 2;271(5644):466–467. doi: 10.1038/271466a0. [DOI] [PubMed] [Google Scholar]
  16. Falconer J. Oral epidermal growth factor is trophic for the stomach in the neonatal rat. Biol Neonate. 1987;52(6):347–350. doi: 10.1159/000242730. [DOI] [PubMed] [Google Scholar]
  17. Feldman E. J., Aures D., Grossman M. I. Epidermal growth factor stimulates ornithine decarboxylase activity in the digestive tract of mouse. Proc Soc Exp Biol Med. 1978 Dec;159(3):400–402. doi: 10.3181/00379727-159-40357. [DOI] [PubMed] [Google Scholar]
  18. GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. George-Nascimento C., Gyenes A., Halloran S. M., Merryweather J., Valenzuela P., Steimer K. S., Masiarz F. R., Randolph A. Characterization of recombinant human epidermal growth factor produced in yeast. Biochemistry. 1988 Jan 26;27(2):797–802. doi: 10.1021/bi00402a046. [DOI] [PubMed] [Google Scholar]
  20. Gonnella P. A., Siminoski K., Murphy R. A., Neutra M. R. Transepithelial transport of epidermal growth factor by absorptive cells of suckling rat ileum. J Clin Invest. 1987 Jul;80(1):22–32. doi: 10.1172/JCI113051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gregory H., Preston B. M. The primary structure of human urogastrone. Int J Pept Protein Res. 1977;9(2):107–118. doi: 10.1111/j.1399-3011.1977.tb03470.x. [DOI] [PubMed] [Google Scholar]
  22. Hall R. A., Widdowson E. M. Response of the organs of rabbits to feeding during the first days after birth. Biol Neonate. 1979;35(3-4):131–139. doi: 10.1159/000241164. [DOI] [PubMed] [Google Scholar]
  23. Harries J. T., Fraser A. J. The acidity of the gastric contents of premature babies during the first fourteen days of life. Biol Neonat. 1968;12(3):186–193. doi: 10.1159/000240105. [DOI] [PubMed] [Google Scholar]
  24. Heath W. F., Merrifield R. B. A synthetic approach to structure-function relationships in the murine epidermal growth factor molecule. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6367–6371. doi: 10.1073/pnas.83.17.6367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Heird W. C., Schwarz S. M., Hansen I. H. Colostrum-induced enteric mucosal growth in beagle puppies. Pediatr Res. 1984 Jun;18(6):512–515. doi: 10.1203/00006450-198406000-00005. [DOI] [PubMed] [Google Scholar]
  26. Hirata Y., Orth D. N. Epidermal growth factor (urogastrone) in human fluids: size heterogeneity. J Clin Endocrinol Metab. 1979 Apr;48(4):673–679. doi: 10.1210/jcem-48-4-673. [DOI] [PubMed] [Google Scholar]
  27. Hock R. A., Hollenberg M. D. Characterization of the receptor for epidermal growth factor-urogastrone in human placenta membranes. J Biol Chem. 1980 Nov 25;255(22):10731–10736. [PubMed] [Google Scholar]
  28. Hock R. A., Nexø E., Hollenberg M. D. Solubilization and isolation of the human placenta receptor for epidermal growth factor-urogastrone. J Biol Chem. 1980 Nov 25;255(22):10737–10743. [PubMed] [Google Scholar]
  29. Hollenberg M. D., Gregory H. Epidermal growth factor-urogastrone: biological activity and receptor binding of derivatives. Mol Pharmacol. 1980 May;17(3):314–320. [PubMed] [Google Scholar]
  30. Hyman P. E., Clarke D. D., Everett S. L., Sonne B., Stewart D., Harada T., Walsh J. H., Taylor I. L. Gastric acid secretory function in preterm infants. J Pediatr. 1985 Mar;106(3):467–471. doi: 10.1016/s0022-3476(85)80682-x. [DOI] [PubMed] [Google Scholar]
  31. Kirkegaard P., Olsen P. S., Poulsen S. S., Nexø E. Epidermal growth factor inhibits cysteamine-induced duodenal ulcers. Gastroenterology. 1983 Dec;85(6):1277–1283. [PubMed] [Google Scholar]
  32. Klagsbrun M., Neumann J. The serum-free growth of Balb/c 3T3 cells in medium supplemented with bovine colostrum. J Supramol Struct. 1979;11(3):349–359. doi: 10.1002/jss.400110310. [DOI] [PubMed] [Google Scholar]
  33. Koldovský O., Thornburg W. Hormones in milk. J Pediatr Gastroenterol Nutr. 1987 Mar-Apr;6(2):172–196. [PubMed] [Google Scholar]
  34. Konturek S. J., Radecki T., Brzozowski T., Piastucki I., Dembiński A., Dembińska-Kieć A., Zmuda A., Gryglewski R., Gregory H. Gastric cytoprotection by epidermal growth factor. Role of endogenous prostaglandins and DNA synthesis. Gastroenterology. 1981 Sep;81(3):438–443. [PubMed] [Google Scholar]
  35. Lebenthal E., Leung Y. K. Epidermal growth factor (EGF) and the ontogeny of the gut. J Pediatr Gastroenterol Nutr. 1987 Jan-Feb;6(1):1–5. [PubMed] [Google Scholar]
  36. MASON S. Some aspects of gastric function in the newborn. Arch Dis Child. 1962 Aug;37:387–391. doi: 10.1136/adc.37.194.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Miclat N. N., Hodgkinson R., Marx G. F. Neonatal gastric pH. Anesth Analg. 1978 Jan-Feb;57(1):98–101. doi: 10.1213/00000539-197801000-00018. [DOI] [PubMed] [Google Scholar]
  38. Moran J. R., Courtney M. E., Orth D. N., Vaughan R., Coy S., Mount C. D., Sherrell B. J., Greene H. L. Epidermal growth factor in human milk: daily production and diurnal variation during early lactation in mothers delivering at term and at premature gestation. J Pediatr. 1983 Sep;103(3):402–405. doi: 10.1016/s0022-3476(83)80412-0. [DOI] [PubMed] [Google Scholar]
  39. Olsen P. S., Nexø E. Quantitation of epidermal growth factor in the rat. Identification and partial characterization of duodenal EGF. Scand J Gastroenterol. 1983 Sep;18(6):771–776. doi: 10.3109/00365528309182093. [DOI] [PubMed] [Google Scholar]
  40. Petrides P. E., Hosang M., Shooter E., Esch F. S., Böhlen P. Isolation and characterization of epidermal growth factor from human milk. FEBS Lett. 1985 Jul 22;187(1):89–95. doi: 10.1016/0014-5793(85)81220-5. [DOI] [PubMed] [Google Scholar]
  41. Pollack P. F., Goda T., Colony P. C., Edmond J., Thornburg W., Korc M., Koldovský O. Effects of enterally fed epidermal growth factor on the small and large intestine of the suckling rat. Regul Pept. 1987 Mar;17(3):121–132. doi: 10.1016/0167-0115(87)90021-8. [DOI] [PubMed] [Google Scholar]
  42. Popliker M., Shatz A., Avivi A., Ullrich A., Schlessinger J., Webb C. G. Onset of endogenous synthesis of epidermal growth factor in neonatal mice. Dev Biol. 1987 Jan;119(1):38–44. doi: 10.1016/0012-1606(87)90204-1. [DOI] [PubMed] [Google Scholar]
  43. Riemen M. W., Wegrzyn R. J., Baker A. E., Hurni W. M., Bennett C. D., Oliff A., Stein R. B. Isolation of multiple biologically and chemically diverse species of epidermal growth factor. Peptides. 1987 Sep-Oct;8(5):877–885. doi: 10.1016/0196-9781(87)90075-1. [DOI] [PubMed] [Google Scholar]
  44. Scheving L. A., Yeh Y. C., Tsai T. H., Scheving L. E. Circadian phase-dependent stimulatory effects of epidermal growth factor on deoxyribonucleic acid synthesis in the duodenum, jejunum, ileum, caecum, colon, and rectum of the adult male mouse. Endocrinology. 1980 May;106(5):1498–1503. doi: 10.1210/endo-106-5-1498. [DOI] [PubMed] [Google Scholar]
  45. Scheving L. A., Yeh Y. C., Tsai T. H., Scheving L. E. Circadian phase-dependent stimulatory effects of epidermal growth factor on deoxyribonucleic acid synthesis in the tongue, esophagus, and stomach of the adult male mouse. Endocrinology. 1979 Dec;105(6):1475–1480. doi: 10.1210/endo-105-6-1475. [DOI] [PubMed] [Google Scholar]
  46. Shing Y. W., Klagsbrun M. Human and bovine milk contain different sets of growth factors. Endocrinology. 1984 Jul;115(1):273–282. doi: 10.1210/endo-115-1-273. [DOI] [PubMed] [Google Scholar]
  47. Ulshen M. H., Lyn-Cook L. E., Raasch R. H. Effects of intraluminal epidermal growth factor on mucosal proliferation in the small intestine of adult rats. Gastroenterology. 1986 Nov;91(5):1134–1140. doi: 10.1016/s0016-5085(86)80008-7. [DOI] [PubMed] [Google Scholar]
  48. Urdea M. S., Merryweather J. P., Mullenbach G. T., Coit D., Heberlein U., Valenzuela P., Barr P. J. Chemical synthesis of a gene for human epidermal growth factor urogastrone and its expression in yeast. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7461–7465. doi: 10.1073/pnas.80.24.7461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Yahav J., Carrion V., Lee P. C., Lebenthal E. Meal-stimulated pepsinogen secretion in premature infants. J Pediatr. 1987 Jun;110(6):949–951. doi: 10.1016/s0022-3476(87)80421-3. [DOI] [PubMed] [Google Scholar]

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