Modification of drug responses in partially hepatectomized rats of either sex by steroids.

Male rats with 2/3 of the liver removed were administered various drugs and chemical agents demonstrated to be stimulatory to the regenerating liver, mainly as supplements in a basal diet and injected with estradiol benzoate daily for the first 9 days p.o. (overall: 250-350 micrograms/kg), the animals being sacrificed on day 10. Estrogen inhibited liver regeneration in many of the drug-treated groups, the restored organ increments often falling to the range of the injected controls on the basal ration. The adult female displayed a lower sensitivity or more inconsistent responses to several drugs, and generally, estrogen had a minor effect on the ensuing restored organ increment. As tested with a few agents, the behavior of adults ovariectomized 21 or 35 days prior to partial hepatectomy simulated that of the males. A group of compounds, including thianthrene and phenyl sulfide, among others, was hepatotrophic to rats of either sex and the increments were not altered by intervention of estrogen. The inhibitory action of estradiol benzoate also extended to males fed the hormone as a dietary supplement. Moderate to high levels of progesterone or testosterone propionate administered to females elicited liver increments much greater than those due to the drugs as such. In contrast to the partially hepatectomized series, the intact male displayed liver enlargement with test agents but except for few, the inhibition due to estrogen was lower. The intact female findings with several drugs appeared to be more consistent as compared to the liver increment data.