ABSTRACT. Epidermal growth factor (EGF) liver receptor ontogeny and somatic growth were studied in mice from day 7 to day 70 postnatally to assess long-term effects of short-term postnatal thyroxine treatment. The mice were given 0.4 pg thyroxinelg body weightlday for the 1st wk of life. EGF receptor binding in liver tissue was studied on days 7, 15, 20, 30, and 70 postnatally. Treated animals had accelerated eyelid opening and tooth eruption, and permanent growth retardation was obvious from the second week of life. Hepatic EGF receptor-binding capacity increased markedly in control mice with increasing age in contrast to a very slow increase in treated mice, making the difference statistically significant (P < 0.01) from day 30. The affinity of EGF receptor binding initially was similar in the two groups of animals (1.09 x lo9 M-' and 1.02 x lo9 M-') and increased by day 30 in controls (2.57 x lo9 M-I), an increase that was not observed in treated animals either at day 30 or 70. These results suggest a sensitive period of imprinting during the first 7 days postnatally, a period when thyroxine can exert a permanent effect on later growth and later hepatic EGF receptor number. (Pediatr Res 23: 557-560, 1988) Abbreviations EGF, epidermal growth factor T4, thyroxine TSH, thyroid-stimulating hormone Thyroid hormones are necessary for postnatal growth and development in rodents as in humans although the mechanism of the thyroid hormone effect is not entirely clear (1). Recent studies suggest that thyroid hormone interaction with specific growth factors may be important for normal postnatal growth and development (2). An interaction with the growth hormonesomatomedin axis has been described (2). Several other growth factors have been studied, but to date the interaction between thyroid hormones and EGF is the best characterized (3,4). EGF is a polypeptide (mouse EGF mol. wt. 6045) first described in extracts from mouse submandibular glands (5-7). In vivo, EGF elicits precocious tooth eruption and eyelid opening in rodents, accelerates lung maturation in lambs and reduces gastric acid secretion in man (4-9). EGF binds to specific plasma membrane receptors that are found in many tissues and significant EGF binding to embryonal tissues has been reported (7,(10)(11)(12)(13)(14) An early indication of a close relation between thyroid hormones and EGF was found by Hamburgh et al. (1 5) who showed that the delay of eyelid opening and tooth eruption observed in hypothyroid animals was reversed by either thyroxine or EGF administration. Further studies suggest that synthesis of both EGF and its receptor protein are influenced by thyroid hormones (3,4,12,(16)(17)(18)(19)(20). Recent studies of early postnatal T4 treatment (0-6 days) of newborn mice have shown a prolonged effect of the T4 on tissue and urine EGF levels and a prolonged effect on growth (21). This effect was not observed in mice treated only during the 2nd wk of life (2 1). The present study was undertaken to relate the disturbances in somatic growth to the postn...