Steroid modulation of liver regeneration and hepatic microsomal enzymes in rats of either sex.

Rats of either sex as intact or partially hepatectomized (two-thirds liver removal) were injected s.c. daily for 7 days post-operatively with natural and synthetic estrogens, androgens or anabolic steroids, progesterone and adrenal cortical hormones and killed on day 10 at which time the livers were processed for microsomal analyses (protein, cytochrome P-450 and enzymes, aminopyrine demethylase and aromatic hydrocarbon or benzo[a]pyrene hydroxylase). Groups were also induced with phenobarbital injected i.p. on the last 3 days at 80 mg/kg each. With the intact males, hexestrol was the only estrogen which caused liver enlargement and at a daily dosage of 1.0 micrograms per rat as well as a decrease in the hydroxylase level. Estradiol benzoate (15 micrograms/rat daily) depressed cytochrome P-450 and the other steroids screened had little effect on the microsomal parameters except for a rise in demethylase with deoxycorticosterone acetate (1.0 mg). A greater sensitivity to estrogens and the other steroid types was noted with the partially hepatectomized males and in the direction of depressions in the microsomal elements, the respective data being expressed as percentages of the controls. Estrogens were better tolerated by the intact female and in general, liver enlargement was remarkable. Microsomal activity was elevated with estradiol benzoate or little affected by estrogens except for depressions in hydroxylase levels with equilin (15 micrograms) and the high dosages of hexestrol and diethylstilbestrol, the last agent also eliciting an increase in cytochrome P-450. No statistically significant effect on the microsomal parameters was observed with the intact female treated with 17-methyltestosterone and the anabolic steroids but decreases occurred on injection with testosterone propionate and the cortical hormones. As with the operated male, partially hepatectomized females exhibited no hepatotrophic response to estrogens and the microsomal changes were moderate with such agents as with the other steroid types and resembling the findings for intact males. Competitive inhibition was followed by Lineweaver-Burke analyses of aminopyrine demethylase in operated females treated with several of the steroids.