EFFECT OF COMBINED TESTOSTERONE AND ESTRADIOL-17-BETA TREATMENT ON THE METABOLISM OF E(2) IN THE PROSTATE AND LIVER OF NOBLE RATS

BACKGROUND. Long-term treatment of Noble (NBL) rats with testosterone (T) and estradiol-17 beta (E(2)) 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 E(2 ) to catechol estrogens (CEs), which are potentially genotoxic, is a m echanism of estrogen carcinogenicity in this tissue. METHODS. Male NBL rats were treated simultaneously with T and E(2), or left untreated, for 16 weeks after which time the liver, VP, and DLP were excised for microsomal preparations. H-3-E(2) metabolites generated in microsomal incubates were separated by high-performance liquid chromatography (HP LC) and identified by coelution with known E(2) metabolites. RESULTS. 2- and 4-hydroxyestrogens were detected at high levels in hepatic micr osomal incubates, and at extremely low levels in prostatic microsomal incubates. T + E(2) treatment of rats did not increase the formation o f these prostatic and hepatic metabolites. CONCLUSIONS. These results do not support CE formation as a mediating step in estrogen-induced tu morigenesis in the rat prostate. (C) 1997 Wiley-Liss, Inc.