Fractionation of female rat serum or plasma on Sephadex G-200 revealed the presence of an activity stimulatory for hepatocyte DNA synthesis. Treatment of female rats with the liver tumor promoter ethinyl estradiol (EE) at 2.5 micrograms/day caused a 1.6 fold increase in the level of this activity at 24 hr in both serum and plasma. The stimulatory activity had a molecular weight of 135 kD, was sensitive to trypsin and heating and was not inhibited by the antiestrogen tamoxifen or antibody to epidermal growth factor (EGF). However, the pooled active fractions from EE-treated rats competed to a greater extent than comparable fractions from control rats for specific [125I]-EGF binding to rat liver membranes. These results demonstrate that treatment of female rats with EE, under conditions known to stimulate liver growth, caused an increase in level of a factor(s) stimulatory for hepatocyte DNA synthesis and whose activity may be mediated through the EGF receptor.
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