Alteration of Insulin Receptor Binding and Protein Kinase Activity in Rat Liver and Placenta by ß-Naphthoflavone

Abstract

Insulin has been shown to be a significant fetal growth factor during late gestation.1,2 The development of insulin receptors in a number of fetal tissues is characterized by an increase in binding activity with gestational age.3–6 Human placenta is a rich source of insulin receptor which has been extensively characterized for its physico-chemical and protein kinase properties.7 Exposure to polyaromatic compounds during pregnancy has been associated with low birth weight in rodents,8,9 monkeys10 and humans.11 This laboratory has found that late feto-placental growth was markedly impaired after the administration of s-naphthoflavone (sNF) and other polyaromatic compounds during mid-gestation.9 Recent evidence suggests an interaction of polyaromatic compounds with growth factor receptors. In human pregnancy, exposure to halogenated aromatic compounds and cigarette smoke has been associated with a decrease in EGF receptor protein kinase activity in the placenta.12 TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) administered to newborn mice decreased EGF binding to liver plasma membranes, increased membrane protein kinase activities and elicited symptoms characteristic of excess EGF.13,14 At present, little is known about the interaction of polyaromatic compounds with other growth factor receptors in development.