Experiments undertaken to investigate the binding of epidermal growth factor by hepatocyte nuclei showed that: (a) isolated nuclei from both normal and regenerating rat liver are capable of binding lzaIepidermal growth factor, (b) the nuclear epidermal growth factopbinding protein is similar in molecular weight to the plasma membrane epidermal growth factor receptor, (c) monoclonal antibodies produced against the plasma membrane epidermal growth factor receptor recognize the nuclear epidermal growth factor receptor and (d) the nuclear receptor has an affinity for epidermal growth factor comparable to that of the plasma membrane receptor, but fewer (-10%) nuclear receptors are available per protein unit compared with the plasma membrane. (HEPATULOGY 199 1; 13: 15-20.)
Over the past decade, evidence has accumulated suggesting that polypeptide hormones and growth factors associate with the nuclei of target cells. This association has been demonstrated by both localization of the hormone/growth factor in nuclei and by detection of specific hormone/growth factor binding sites (presumably receptors) on or in nuclei (1).
Epidermal growth factor (EGF) is one growth factor whose nuclear association has been clearly demonstrated. The accumulation of endocytosed EGF within cell nuclei was first demonstrated in cultured rat pituitary cells (2) and later in bovine corneal and granulosa cells (3). In these studies, the nuclear accumulation of EGF was induced by the exposure of cells to chloroquine or leupeptin, inhibitors of the normal lysosomal degradation of EGF. EGF has been shown to accumulate in the nuclei of rat epidermis and hair follicle