Evidence for modulation of hepatic mass by estrogens and hepatic "feminization"

Animals with end-to-side portacaval shunts and sham-operated animals, wherein the body weight and liver weight of the animals varied spontaneously over a considerable range, were studied. The relationships between hepatic androgen- and estrogen-receptor content, serum testosterone and estradiol levels and hepatic mass were characterized. Animals with portacaval shunts were smaller than those without shunts. Moreover, they had reduced serum levels of testosterone and estradiol. The reduction in serum testosterone was greater than that of estradiol. As a result, the calculated estrogen/testosterone ratio of the two groups of animals was greater for the portacaval shunt animals than for the controls. The dissociation constant values for the androgen receptor and estrogen receptor in the liver did not differ between groups. The activity of the androgen receptor (p less than 0.01) and estrogen receptor (p less than 0.05) was reduced markedly in the animals with portacaval shunts compared with controls. Moreover, the hepatic cytosolic estrogen receptor activity--but not that of the androgen receptor--correlated with the measured hepatic mass in both groups of animals. These data suggest that hepatic feminization is either associated with or is a hepatic regenerative signal in the rat.