Epidermal growth factor in the developing mammal.

EGF has been characterized as an important growth factor in mammalian development and function, but its precise roles and significance are not yet clear. EGF may have a role in embryogenesis and fetal 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 TGF, subserves a developmental role in the fetus. The mRNA for alpha TGF has been demonstrated in the fetus [22] and alpha TGF acts via EGF receptors. In the postnatal animal EGF mRNA, immunoreactive 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 urine EGF in the maintenance of stomal, gut and urinary epithelial surface integrity seems likely, although not yet proven. Many other tissues presumably produce EGF, and tissue EGF concentrations (and probably synthesis) are hormone responsive in many tissues. Thyroid and gonadal steroid hormones have been shown to influence EGF and/or EGF receptors in various tissues, and EGF, probably acting largely through autocrine or paracrine routes, 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 in many laboratories. Figure 3 summarizes these concepts.