Role of glucocorticoids and epidermal growth factor in normal and abnormal palatal development

The purpose of this chapter has been to discuss glucocorticoid and EGF involvement in normal and abnormal palatal development. It is to be hoped that we have made clear the important point that these hormone/growth factors and their receptors are present during normal embryonic palatal development to provide for regulation of growth and cellular differentiation. When these hormone/growth factors are administered in pharmacological or large doses that result in teratogenesis, these potent chemicals and their receptors then become inducers of cleft palate. The primary reason for this is that the hormone/growth factor receptors have unique and special areas of localizations in target (embryonic and fetal) tissues, e.g., glucocorticoids in the palate. Therefore, large amounts of these chemicals are specifically bound to receptors in these target tissues and these high levels of hormone/growth factor-receptor complexes result in aberrant development, e.g., glucocorticoids cause inhibition of palatal mesenchymal cell growth. These effects are distinct from the interactions of physiological levels of these hormone/growth factors with their receptors in these target tissues during development, e.g., glucocorticoids cause induction of key enzymes and modulation of EGF receptor levels. The exact molecular mechanism(s) by which high levels of hormone/growth factors--receptor complexes exert harmful effects on embryos or fetuses is (are) unknown and remain(s) a challenge for the future. Interaction of hormone/growth factors and their receptors certainly cannot provide an explanation for the mechanism of all types of craniofacial teratogenesis, but this concept certainly appears capable of providing important information relating to the mechanisms of many animal and human teratogens. The fact that these chemicals and their receptors are involved in normal development makes them all the more important since subtle alterations in their levels or activities could result in teratogenesis without an exposure to pharmacological levels of these hormone/growth factors. It seems that progress in this area will develop quickly since the techniques of recombinant DNA research are available in conjunction with responsive in vitro cell systems such as the established line of human embryonic palatal mesenchymal cells. Clearly, the future looks very exciting for understanding the role that these hormone/growth factors and their receptors play in normal and abnormal palate development.