The influence of steroidal and nonsteroidal estrogens on the 5 alpha-reduction of testosterone by the ventral prostate of the rat.

The 5 alpha-reduction of testosterone to dihydrotestosterone (DHT) correlates with the androgen-mediated growth of the prostate under different experimental and clinical conditions. The aim was to study the regulation of the prostatic growth and enzyme activity by steroidal and nonsteroidal estrogens. Estrogens did not activate the androgen-dependent 5 alpha-reductase activity in cultured prostate of the rat. The direct inhibition of the enzyme activity by estrogens at the concentrations achievable in the male is not probable either. However, early estrogenization of the male rats in utero (on Day 17 of pregnancy) with diethylstilbestrol (DES) resulted in a persistent decrease of the enzyme activity and growth of the prostate indicating a critical estrogen-sensitive period in the regulation of the ultimate enzyme activity. The similar DES-like inhibitory effect on the growth of the prostate was achieved by keeping animals from fertilization throughout the pregnancy until weaning on diet containing soy, rich in environmental estrogens. Zearalenone (Zeranol) and coumestrol, two nonsteroidal estrogens found in human and animal food mimicked estradiol action in culture, but they were not estrogenic or antiestrogenic when administered to normal adults.

The metabolism of arachidonic acid in isolated rat lungs is not changed during cigarette smoke ventilation.

Cigarette smoke ventilation of isolated perfused rat lungs partially inhibited the pulmonary vascular pressor response to arachidonic acid. The amounts of metabolites of exogenous arachidonic acid in the perfusion effluent remained unchanged during smoke ventilation. The antiaggregatory effect of the effluent during pulmonary infusion of AA was not decreased by smoke ventilation. The cause of the previously reported increased platelet aggregation after smoking remains unclear.

Dietary cholesterol-induced changes of xenobiotic metabolism in liver. I. Influence of xenobiotic administration on hepatic membrane structure.

We have studied the effects of dietary lipids on the structure and function of hepatic endoplasmic reticulum by feeding rats either with a 2% cholesterol or cholesterol-free diet. Rats were further administered either phenobarbitone, carbon tetrachloride, or both in combination to reveal possible differences in the response of the microsomal membranes to xenobiotics. Cholesterol feeding increased the membrane cholesterol contents and also carbon tetrachloride increased microsomal cholesterol contents in those rats fed a cholesterol-free diet. Also the microsomal phospholipid contents were higher in those rats fed 2% cholesterol diet than in those fed cholesterol-free diet and in the 2% cholesterol group also phenobarbitone increased the phospholipid contents. In addition, there were changes in the phospholipid-fatty acid proportions between rats fed 2% cholesterol and cholesterol-free diets. When 1,8-ANS was used as a fluorescence probe, phenobarbitone increased the fluorescence in both the dietary groups, while carbon tetrachloride decreased it; less change was present using PNA as a substrate. When Scatchard plots were constructed phenobarbitone changed the turning point more in the cholesterol-free group than in the 2% cholesterol group, while reversed orders of changes were found with carbon tetrachloride. The results demonstrated that dietary cholesterol has profound effects on the structure of microsomal membranes far beyond changes in their cholesterol content. The membrane fluidity also changes owing to alterations in the phospholipid contents and in their fatty acid composition.

Absorption and metabolism of intratracheally instilled cortisol and beclomethasone dipropionate in the isolated perfused rat lungs.

The fate of [4-14C]-cortisol and [16,16 alpha-3H]-beclomethasone dipropionate following intratracheal application of the substrates into isolated perfused rat lungs was studied. Both substrates were transferred to the perfusion medium, cortisol at a much higher rate than beclomethasone dipropionate. The proportion of different metabolites of the total radioactivity was larger with beclomethasone dipropionate in both the perfusion medium and the lung tissue. The lungs are considered to have a catabolic role in cortisol metabolism.

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the hepatic metabolism of testosterone in the rat.

A dose of 20 micrograms/kg of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was given to adult male rats intragastrically and the metabolism of [4-14C]-testosterone by liver homogenate was examined 1 week later. The overall catabolism of testosterone was significantly reduced by the TCDD treatment. Dihydroxysteroids (intermediate reduced metabolites) were increased, while the production of polar non-conjugated metabolites (end products) was diminished.