Sex Difference in Epidermal Growth Factor Receptor Levels in Rat Liver Plasma Membrane*

The specific binding of [125I]epidermal growth factor [( 125I]EGF) to hepatic microsomal membranes was about 2-fold higher in adult male than in adult female rats. Scatchard analysis of the binding data showed that the sex difference in EGF binding was due to the difference in EGF receptor concentration rather than to a change in receptor affinity. From the developmental study, an apparent sex difference in EGF binding was observed from the pubertal period (4 weeks of age). Castration of adult male rats slightly, but significantly, decreased the EGF receptor level; and moreover, treatment of adult females with testosterone increased it only slightly. On the other hand, castration of neonatal male rats decreased the EGF receptor content almost to the female level. The decreased level of the receptor was completely restored by the combination of neonatal and pubertal treatments with testosterone. Neonatal or pubertal treatment alone of castrated animals had no significant effect on the decreased level of EGF receptors. These effects of testosterone were similarly observed when normal female rats were treated with the steroid. Moreover, hypophysectomy of the rats resulted in the marked decrease in EGF receptors only in the male animals. Treatment of hypophysectomized rats with either testosterone or T3 had no apparent effect on the EGF receptors. The membrane protein, cross-linked with [125I]EGF, had a mol wt of 170,000, and this protein (EGF receptor) was phosphorylated basally or by the addition of EGF. The rate of affinity labeling, or phosphorylation of EGF receptors, was in good agreement with the results of the EGF binding study. These results strongly suggest that the EGF receptor level in rat liver plasma membranes is in part regulated by the hypothalamopituitary unit and that neonatal androgens are essential for this regulation, probably through their effects on the hypothalamus.