Effect of combined testosterone and estradiol-17 beta treatment on the metabolism of E2 in the prostate and liver of noble rats.

Background: Long-term treatment of Noble (NBL) rats with testosterone (T) and estradiol-17 beta (E2) induces dysplasia in the dorsolateral lobe (DLP) but not in the ventral lobe (VP) of the rat prostate. The aim of this study was to determine whether metabolic conversion of E2 to catechol estrogens (CEs), which are potentially genotoxic, is a mechanism of estrogen carcinogenicity in this tissue.
Methods: Male NBL rats were treated simultaneously with T and E2, or left untreated, for 16 weeks after which time the liver, VP, and DLP were excised for microsomal preparations. 3H-E2 metabolites generated in microsomal incubates were separated by high-performance liquid chromatography (HPLC) and identified by coelution with known E2 metabolites.
Results: 2- and 4-hydroxyestrogens were detected at high levels in hepatic microsomal incubates, and at extremely low levels in prostatic microsomal incubates. T + E2 treatment of rats did not increase the formation of these prostatic and hepatic metabolites.
Conclusions: These results do not support CE formation as a mediating step in estrogen-induced tumorigenesis in the rat prostate.