Systemic treatment with epidermal growth factor causes organ growth concomitant with reduced circulating levels of IGF-I and IGFBP-3: time-dependent changes in female rats

Abstract

Systemic treatment with epidermal growth factor (EGF) in neonatal rats reduces circulating levels of insulin-like growth factor I (IGF-I) and causes somatic growth retardation. In this study, we investigated the effects of EGF treatment on the IGF system and on visceral organ growth and longitudinal growth in mature rats. We treated female Wistar rats for 0 (n = 16), 1 (n = 8), 2 (n = 8), 3 (n = 8), or 4 (n = 8) weeks with subcutaneous EGF (150 microg/kg/day). The animals were weighed once a week. At sacrifice, various viscera were removed and weighed. Blood and serum samples obtained at sacrifice were analysed for growth hormone (GH), IGF-I, IGF binding proteins (IGFBPs) and various routine parameters. EGF treatment increased the total body weight. All parts of the gastrointestinal tract, the liver, the pancreas, the spleen, the bladder, the suprarenal glands and the ovaries increased proportionately more in weight than the increase in total body weight; the heart and the kidneys increased proportionately in weight whereas the weight of the perirenal fat was reduced. There were no changes in tail length but the mean length of the tibia was slightly increased in the group treated for 4 weeks with EGF. Circulating GH was unchanged but IGF-I and IGFBP-3 were reduced approximately 25 and 45%, respectively, in all EGF treated groups. There were no changes in the hepatic content of IGF-I and IGFBPs. In conclusion, systemic EGF treatment causes visceral growth concomitant with reduced circulating levels of IGF-I and IGFBP-3 in mature female rats.