Sex hormone receptors were quantitated in normal male rat liver and in regenerating liver at several different times after partial (70%) hepatectomy. Both estrogen and androgen receptor content were altered dramatically by partial hepatectomy. Total hepatic content and nuclear retention of estrogen receptors increased, with the zenith evident 2 days after partial hepatectomy, corresponding to the zenith of mitotic index. Serum estradiol increased after 1 day, and reached a maximum at 3 days after surgery. In contrast, total and nuclear androgen receptor content demonstrated a massive decline at 1, 2, and 3 days after resection. Serum testosterone displayed a parallel decline. In addition, hepatic content of two androgen-responsive proteins was reduced to 15% and 13% of normal values during this period. The activity of these various proteins during regeneration of male rat liver is comparable to that observed in the liver of normal female rats. Taken together, these results indicate that partial hepatectomy induces a feminization of certain sexually dimorphic aspects of liver function in male rats. Furthermore, these data provide evidence that estrogens, but not androgens, may have an important role in the process of liver regeneration.Mammalian liver of both sexes is responsive to sex hormones. Liver is estrogen responsive in that it contains receptors for this hormone and responds by the synthesis of specific proteins (reviewed in Reference 1). Liver contains androgen receptors as well (2-5). In fact, the sexually dimorphic hepatic content of certain receptors and microsomal enzymes observed in male rats is maintained by testosterone (reviewed in References 1 and 6). Ultimate control over these sex differences in hepatic function resides in the pituitary gland. In particular, growth hormone secretion patterns, also sexually dimorphic in nature, appear to regulate hepatic levels of many microsomal steroid and drug metabolizing enzymes as well as steroid receptor levels (1,7,8).Since Higgins and Anderson originally reported (9) the technique of partial hepatectomy (PH) in rats, investigators have been studying the effect of hepatic resection and the remnant liver with the goal of identifying the mechanisms that regulate hepatic regeneration. During the last 10 yr, hormones have assumed a prominent role as factors related in some way to hepatic regeneration after PH. It has been suggested that hormonal agents such as insulin, glucagon, and epidermal growth factor may initiate the process of regeneration (10-17); however, other hormones such as parathyroid hormone (18) (23). These data demonstrated that the proliferative activity of the regenerating liver is concurrent with a significant increase in nuclear localization of hepatic ERs. However, this study did not examine possible increases in serum estradiol content that might account for the increased nuclear ER localization, nor was total hepatic content of ER examined. We have now extended the study to answer these questions, and in addition, to determin...