A rat hepatic cytosolic [3H]methyltrienolone (R1881) binding protein was studied under various conditions. This protein was also compared with the male-specific high capacity--low affinity estrogen-binding protein derived from the same cytosolic fraction. Analysis of the R1881 binding protein in adult (60-85 days old) male rat liver cytosol indicated the presence of a high affinity--low capacity binding site (Kd = 0.3 nM; Bmax = 5.9 fmol/mg) and a lower affinity--higher capacity component (Kd = 10.4 nM; Bmax = 131 fmol/mg). The latter component was eliminated by addition of triamcinolone or cortisol to the assay mixture. Steroid binding to the high affinity R1881 site was specific for testosterone, dihydrotestosterone, androstenedione, and mibolerone, with a moderate specificity to cyproterone acetate, flutamide hydroxide, and estradiol. Saturation studies indicated that these steroids were binding to the same or a similar high affinity component except for flutamide hydroxide which produced nonsaturable displacement. The high affinity site had no specificity for progesterone, diethylstilbestrol, or cortisol. Like the high capacity--low affinity protein, this protein was not present in the immature, adult, or 10-day ovariectomized adult female. However, unlike the high capacity--low affinity protein, it was present in low quantities in the immature male. In addition, castration of the adult for 18 h, 4 days, or 10 days or hypophysectomy for 10-17 days did not have a significant effect on the high affinity component compared with the controls. Testosterone administration to these animals did not alter this protein binding. These studies indicate that a specific, high affinity--low capacity androgen-binding protein exists in rat hepatic cytosol. Furthermore, this protein shows age and sex dependency, but its presence is not affected by altering gonadal or hypophyseal factors in the adult male.

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Female Wistar rats were fed a liquid diet, Sustacal, which contained ethanol (40% of calories) or isocaloric sucrose. Mestranol and norethindrone in pharmacological doses were also administered via this diet. Hepatic microsomal benzo[a]pyrene (BP) hydroxylase, epoxide hydrase, aniline hydroxylase, and aminopyrine-N-demethylase activities were measured after 3 and 6 months treatment. In addition, hepatic histology and electron microscopic studies were carried out in an attempt to monitor ethanol-associated fat accumulation in the central vein region. Mestranol or norethindrone alone for 3 months produced an elevation of BP hydroxylase activity which was no longer present after 6 months treatment. When compared with the 3-month time period, BP hydroxylase activity was significantly decreased in livers of animals which had ingested ethanol (group 10 vs. group 2), ethanol plus mestranol (group 12 vs. group 4), and ethanol plus norethindrone (group 14 vs. group 6) for 6 months. However, in the steroid-treated groups, the ethanol associated decreases were not as large as that seen without ethanol over the 3-month time period (group 11 vs. group 3; group 13 vs. group 5). No decrease was observed in the combined steroid plus ethanol-treated groups. Ethanol treatment for 6 months increased hepatic epoxide hydrase activity in both the nonsteroid and mestranol-treated group. Aniline hydroxylase was increased by ethanol in the combined steroid-treated animals. Otherwise there were no significant changes in the enzyme activities measured. Hepatic histology studies carried out on the 6-month ethanol-treated animals provided evidence of fat accumulation in the central vein region of the liver lobule, as expected. However, the steroid- plus ethanol-treated groups exhibited less apparent fat accumulation in the central vein region. These data do not support the hypothesis that mestranol and (or) norethindrone will accentuate the inhibition of liver BP hydroxylase or the central vein fat accumulation produced by chronic ethanol ingestion in the female rat.

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