Estrogen and androgen receptors within the liver have been reported to modulate the hepatic regenerative response to partial hepatectomy. Moreover, cyclosporine has several untoward effects that might occur as a consequence of alterations in sex hormone activity. To evaluate these questions the following experiments were performed. Estrogen and androgen receptors in cytosol were quantitated in livers of rats treated with cyclosporine or olive oil vehicle before and after partial hepatectomy or a sham operation. Ornithine decarboxylase activity and thymidine kinase activity were assessed as indices of hepatic regeneration. Preoperative levels of estrogen receptor activity in the hepatic cytosol were significantly greater in rats treated with cyclosporine as compared to vehicle treated controls (P < 0.01). In contrast, preoperative levels of androgen receptor activity in the cyclosporine-treated and vehicle-treated animals were similar. Following partial hepatectomy, a reduction in the activity of both sex hormone receptors in the hepatic cytosol was observed and was compatible with results described previously in normal animals. Unexpectedly the preoperative levels of ornithine decarboxylase (P < 0.01) and thymidine kinase activity (P < 0.01) were significantly greater in the rats treated with cyclosporine as compared to the vehicle treated controls. As expected, ornithine decarboxylase activity (at 6 hr) and thymidine kinase activity (at 24 hr) rose and peaked in response to a partial hepatectomy but were significantly greater (P < 0.05) in the rats treated with cyclosporine as compared to the vehicle. These results show that cyclosporine treatment causes an increase in the hepatic content of estrogen receptor activity that is associated with an enhanced potential for a regenerative response. These effects of cyclosporine treatment on the sex hormone receptor lvels in liver may explain the mechanisms responsible for some of the untoward effects of treatment with this agent.
Keywordscyclosporine; estrogen; androgen; hepatectomy; cytosol The presence and properties of sex hormone receptors in the liver have been studied extensively (1). However, the precise function of these receptors within the liver is unknown. Nonetheless, in mammals certain functions of the liver are known to display a sexual dimorphism (2-4). Testosterone, present in utero and after puberty, appears to be the major determinant of the differences between the sexes in hepatic function. Hepatic regeneration following a partial hepatectomy is associated with a "feminization" of the liver in male rats as manifested by an increase in the serum level of estradiol and the hepatic activity of estrogen receptors. Moreover a reduction in the serum level of testosterone and the activity of the androgen receptors within the liver occurs (1,5). Translocation of estrogen receptors from the cytosol to the nucleus in liver subjected to a prior partial hepatectomy coincides with the initiation of DNA synthesis. These observations suggest an important r...