Epidermal growth factor-induced growth retardation in the newborn rat: quantitation and relation to changes in skin...

Somatic growth retardation was studied in neonatal Sprague-Dawley rats following treatment with exogenous epidermal growth factor (EGF). Dose-response data are presented for the first 2 days of postnatal life relating log EGF dose (range 50 to 1000 ng per gram body weight) to incremental daily weight gain. Regression analysis indicated that the effect of EGF to retard somatic growth was not cumulative, and, in fact, the same dose of EGF had less effect on the second day of life than on the first. Concomitant with its ability to retard growth, EGF elicited a transient cutaneous reaction characterized by a marked alteration in skin viscoelasticity and temperature. Neonatal rats treated with exogenous EGF exhibited: (1) a dose-dependent reduction in skin redundancy measured by decrease in the height of the dorsal skinfold; (2) a diminution in integumental water content determined by wet weight/dry weight ratios and relative tissue specific gravities; and (3) a rapid fall in midscapular skin temperature within 60 minutes of systemic administration of EGF. Both the EGF-elicited cutaneous reaction and the ability of EGF to retard somatic growth disappeared by the end of the second week of life. Administration of human biosynthetic EGF resulted in responses identical to the purified mouse protein. In summary, the pharmacological effects of EGF to retard somatic growth in the newborn rodent are confined to the immediate neonatal period and are preceded by transient alteration in skin temperature and cutaneous biomechanical properties.