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Horm Metab Res 2002; 34(1): 16-20
DOI: 10.1055/s-2002-19961
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© Georg Thieme Verlag Stuttgart · New York

Hepatocyte Growth Factor in Human Breast Milk Acts as a Trophic Factor

H.  Itoh 1 , A.  Itakura 1 , O.  Kurauchi 2 , M.  Okamura 1 , H.  Nakamura 3 , S.  Mizutani 1
  • 1Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Tsurumai-cho, Showa-ku, Nagoya, Japan
  • 2Department of Obstetrics and Gynecology, Nagoya Daini Red Cross Hospital Myoken-cho, Showa-ku, Nagoya, Japan
  • 3Maternity and Perinatal Care Center, Nagoya University Hospital, Tsurumai-cho, Showa-ku, Nagoya, Japan
Further Information

Publication History

5 June 2001

19 September 2001

Publication Date:
14 August 2002 (online)

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Abstract

To evaluate the significance of hepatocyte growth factor (HGF) in milk in the perinatal period, we examined immunoreactive HGF levels and bioactivity in human milk. Human milk samples were obtained from women at various postpartum ages, and the levels of HGF were measured by ELISA. In the cross sectional study, the concentration of milk HGF from term deliveries showed a significant inverse correlation with progress of lactation, whereas in cases of preterm delivery concentrations, levels remained high after a long period of lactation. In the longitudinal analysis, the contents of HGF in colostrum, transitional, and mature milk from preterm deliveries were significantly be higher than those from term deliveries. Although mature milk from term and preterm deliveries contained significantly lower levels of HGF than colostrum, high levels of HGF persisted in mature milk from preterm deliveries. After partial purification, immunoblotting analysis showed the presence of both α- and β-chains of HGF. HGF in milk stimulated proliferation of rat hepatocytes in primary culture, which was inhibited by supplementation with anti-HGF antibody. Thus, a high concentration of bioactive HGF is present in human milk in the postpartum period. Our results suggest that HGF in milk acts as a trophic factor for the gastrointestinal tract in neonates.

Key words

Hepatocyte Growth Factor - Preterm Milk - Colostrum - Trophic Factor

References

  • 1 Grosvenor C E, Picciano M F, Baumrucker C R. Hormones and growth factors in milk.  Endocr Rev. 1992;  14 710-728
    PubMedGoogle Scholar
  • 2 Berseth C L. Enhancement of intestinal growth in neonatal rats by epidermal growth factor in milk.  Am J Physiol. 1987;  253 G662-665
    PubMedGoogle Scholar
  • 3 Carpenter G. Epidermal growth factor is a major growth-promoting agent in human milk.  Science. 1980;  210 198-199
    PubMedGoogle Scholar
  • 4 Birchmeier C, Gherardi E. Developmental roles of GFD/SF and its receptor, the c-Met tyrosine kinase.  Trends Cell Biol. 1998;  8 404-409
    CrossrefPubMedGoogle Scholar
  • 5 Furugori K, Kurauchi O, Itakura A. et al . Levels of hepatocyte growth factor and its messenger ribonucleic acid in uncomplicated pregnancies and those complicated by preeclampsia.  J Clin Endocrinol Metab. 1997;  82 2726-2730
    CrossrefPubMedGoogle Scholar
  • 6 Itakura A, Kurauchi O, Morikawa S. et al . Involvement of hepatocyte growth factor in formation of broncho-alveolar structure in embryonic rat lung in primary culture.  Biochem Biophys Res Commun. 1997;  241 98-103
    CrossrefPubMedGoogle Scholar
  • 7 Matsumoto K, Nakamura T. Hepatocyte growth factor (HGF) as a tissue organizer for organogenesis and regeneration.  Biochem Biophys Res Commun. 1997;  239 639-644
    CrossrefPubMedGoogle Scholar
  • 8 Tajima H, Matsumoto K, Nakamura T. Regulation of cell growth and motility by hepatocyte growth factor and receptor expression in various cell species.  Exp Cell Res. 1992;  202 423-431
    CrossrefPubMedGoogle Scholar
  • 9 Takahashi M, Ota S, Shimada T. et al . HGF is the most potent endogenous stimulant of rabbit gastric epithelial cell proliferation and migration in primary culture.  J Clin Invest. 1995;  95 1994-2003
    PubMedGoogle Scholar
  • 10 Fukamachi H, Ichinose M, Tsukada S. et al . Hepatocyte growth factor region specifically stimulates gastro-intestinal epithelial growth in primary culture.  Biochem Biophys Res Commun. 1994;  205 1445-1451
    CrossrefPubMedGoogle Scholar
  • 11 Horibe N, Okamoto T, Itakura A. et al . Levels of hepatocyte growth factor in maternal serum and in amniotic fluid.  Am J Obstet Gynecol. 1995;  173 937-942
    CrossrefPubMedGoogle Scholar
  • 12 Kurauchi O, Itakura A, Ando H, Kuno N, Mizutani S, Tomoda Y. The concentration of hepatocyte growth factor in human amniotic fluid at second trimester: relation to fetal birth weight.  Horm Metab Res. 1995;  27 335-338
    PubMedGoogle Scholar
  • 13 Okamura M, Kurauchi O, Itakura A. et al . Hepatocyte growth factor in human amnionic fluid promotes the migration of fetal small intestinal epithelial cells.  Am J Obstet Gynecol. 1998;  178 175-179
    PubMedGoogle Scholar
  • 14 Itakura A, Kurauchi O, Morikawa S, Furugori K, Mizutani S, Tomoda Y. Human amniotic fluid motogenic activity for fetal alveolar type II cells by way of hepatocyte growth factor.  Obstet Gynecol. 1997;  89 729-733
    CrossrefPubMedGoogle Scholar
  • 15 Pepper M S, Soriano J V, Menoud P A, Sappino A P, Ora L, Montesano R. Modulation of hepatocyte growth factor and c-met in the rat mammary gland during pregnancy, lactation, and involution.  Exp Cell Res. 1995;  219 204-210
    CrossrefPubMedGoogle Scholar
  • 16 Niranjan B, Buluwela L, Yant J. et al . HGF/SF: a potent cytokine for mammary growth, morphogenesis and development.  Development. 1995;  121 2897-2908
    PubMedGoogle Scholar
  • 17 Soriano J, Pepper M S, Nakamura T, Orci L, Montesano R. Hepatocyte growth factor stimulates extensive development of branching duct-like structures by cloned mammary gland epithelial cells.  J Cell Sci. 1995;  108 413-430
    PubMedGoogle Scholar
  • 18 Yang Y, Spitzer E, Meyer D. et al . Sequential requirement of hepatocyte growth factor and neuregulin in the morphogenesis and differentiation of the mammary gland.  J Cell Biol. 1995;  131 215-226
    CrossrefPubMedGoogle Scholar
  • 19 Tsubouchi H, Niitani Y, Hirono S. et al . Levels of the human hepatocyte growth factor in serum of patients with various liver diseases determined by an enzyme-linked immunosorbent assay.  Hepatology. 1991;  13 1-5
    CrossrefPubMedGoogle Scholar
  • 20 Ando H, Kasugai M, Ishihara Y. et al . Enhanced proliferation of fetal rat hepatocytes in primary culture induced by ritodrine.  Am J Obstet Gynecol. 1993;  168 693-697
    PubMedGoogle Scholar
  • 21 Nakamura T, Nawa K, Ichihara A, Kaise N, Nishino T. Purification and subunit structure of hepatocyte growth factor from rat platelets.  FEBS Lett. 1987;  224 311-316
    CrossrefPubMedGoogle Scholar
  • 22 Yamada Y, Saito S, Morikawa H. Hepatocyte growth factor in human breast milk.  Am J Repro Immunol. 1998;  40 112-120
    PubMedGoogle Scholar
  • 23 Srivastava M D, Lippes J, Snvastava B IS. Hepatocyte growth factor in human milk and reproductive tract fluids.  Am J Repro Immunol. 1998;  42 347-354
    PubMedGoogle Scholar
  • 24 Lucas A, Cole T J. Breast milk and neonatal necrotizing enterocolitis.  Lancet. 1990;  336 1519-1523
    Google Scholar
  • 25 Jansson L, Karlson F A, Westermark B. Mitogenic activity and epidermal growth factor content in human milk.  Acta Paediatr Scand. 1985;  74 250-253
    PubMedGoogle Scholar
  • 26 Hofmann G E, Abramowicz J S. Epidermal growth factor (EOF) concentrations in amniotic fluid and maternal urine during pregnancy.  Acta Obstet Gynecol Scand. 1990;  69 217-221
    PubMedGoogle Scholar
  • 27 Uauy R D, Fanaroff A A, Korones S B. et al . Necrotizing enterocolitis in very low birth weight infants: biodemographic and clinical correlates.  J Pediatr. 1991;  119 630-638
    CrossrefPubMedGoogle Scholar
  • 28 Gross S J, David R J, Bauman L. et al . Nutritional composition of milk produced by mothers delivering preterm.  J Pediatr. 1980;  96 641-646
    PubMedGoogle Scholar
  • 29 Genzel-Boroviczeny O, Wahle J, Koletzko B. Fatty acid composition of human milk during the 1st month after term and preterm delivery.  Eur J Pediatr. 1997;  156 142-147
    CrossrefPubMedGoogle Scholar
  • 30 Gross S J, David R J, Bauman L, Tomarelli R M. Nutritional composition of milk produced by mothers delivering preterm.  J Pediatr. 1980;  96 641-644
    PubMedGoogle Scholar
  • 31 Jam N, Mathur N B, Sharma V K, Dwarkadas A M. Cellular composition including lymphocyte subsets in preterm and full term human colostrum and milk.  Acta Pediatr Scand. 1991;  80 395-399
    PubMedGoogle Scholar
  • 32 Niranjan B, Buluwela L, Yant J. et al . HGF/SF: a potent cytokine for mammary growth, morphogenesis and development.  Development. 1995;  121 2897-2908
    PubMedGoogle Scholar

A. Itakura, M.D.

Department of Obstetrics and Gynecology · Nagoya University School of Medicine

65 Tsurumai-cho · Showa-ku · Nagoya 466-8550 · Japan

Phone: + 81 (52) 744-2261

Fax: + 81 (52) 744-2268

Email: aita@med.nagoya-u.ac.jp

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