2.3. Epidermal growth factor

Epidermal growth factor (EGF) has been characterized as an important growth factor in mammalian development and function, but its precise role is not yet completely clear (BEARDMORE and RICHARDS, 1983). The ingestion of natural species-specific milk causes dramatic enhancement of visceral and somatic growth (BERSETH, 1987b; BERSETH, LICHTENBERGER and MORRIS, 1983; HEIRD, SCHWARZ and HANSEN, 1984) and may also influence intestinal enzyme maturation in several mammalian species (YEH and HOLT, 1985).

The mitogenic effect of human milk can be blocked by EGF-specific antibodies (CARPENTER, 1980). Furthermore, EGF has been shown to enhance growth, differentiation and maturation of rodent intestine (MOORE et al., 1986). The EGF in breast milk remains structurally intact and biologically active after gastric passage (THORNBURG et al., 1984). EGF most likely has a role in embryogenesis and organ growth, since receptors have been identified in fetal tissues. However, EGF mRNA has not been shown in the fetus, and it seems likely that the related peptide, alpha-transforming growth factor (TGF), serves a developmental role in the fetus. The mRNA for TGF has been demonstrated in the fetus (BERSETH, 1987a), and TGF acts via EGF receptors. In the post-natal animal, EGF mRNA, immuno-reactive EGF, and EGF receptors are present in many tissues.

In the rodent, the highest levels of EGF mRNA are found in the salivary glands and kidneys, and EGF is secreted in large amounts in saliva and urine. A role for salivary and urinary EGF in the maintenance of stomal, gut and urinary epithelial surface integrity seems likely although not yet proven (DEMBINSKY and JOHNSON, 1985). Many other tissues presumably produce EGF, and tissue EGF concentrations (and probably synthesis) are hormone-responsive in many tissues. The trophic effects of EGF have been potentiated by retinoic acid (WIDDOWSON, COLOMBO and ARTAVANIS, 1976), prostaglandins (KONTUREK et al., 1981) and thyroxine (LAKASHMANAN et al., 1985), all of which are present in breast milk.

Thyroid and gonadal steroid hormones have been shown to influence EGF and/or EGF receptors in various tissues (LAKASHMANAN et al., 1985). EGF can exert mitogenic or developmental actions autonomously or in response to hormonal signals. An endocrine role also is likely but of secondary importance, as is the case for the insulin-like growth factors. The precise details of these EGF actions and effects in immature and adult animals are being explored further in many laboratories.