Up-regulation of nuclear IGF-I receptor by short term exposure of stilbene estrogen, diethylstilbestrol.

In the present study we report the novel findings that IGF-I receptors are present in the nucleus based on the evidence from binding assay, detection of receptors by affinity labeling and Western blotting, and localization by immunofluorescence. The level of nuclear IGF-I receptors (nIGF-IRs) almost doubled in stilbene estrogen (diethylstilbestrol, DES) treated hamster kidneys compared to the controls. The binding constants Kd and Bmax of nIGF-IR of controls, 22.1 nM and 6.6 nmol/mg protein, respectively, were changed in response to DES treatment to 5.3 nM and 16.3 nmol/mg protein (P < 0.001), respectively. The enhanced level of IGF-IR in DES-treated nuclei was confirmed by both affinity labeling and Western blotting. These data suggest that IGFs may exert their biological effect through the IGF-I receptor present in the nucleus. Whether the up-regulation of nIGF-IR by exposure to a carcinogenic dose of DES may be a factor in the induction of renal cancer in Syrian hamsters, is not clear.