In vivo metabolism of testosterone-3H in R-3327, an androgen-sensitive rat prostatic adenocarcinoma.

Abstract

A spontaneous prostatic adenocarcinoma (R-3327) of a Copenhagen rat has been maintained for 14 generations by s.c. transplantations to Copenhagen and F1 hybrid hosts. The tumor remains histologically a well-differentiated adenocarcinoma. In order to study the role of gonadal hormones in this system, tumor explants were inoculated to intact males, castrated males, and intact females, and the growth of the explants was followed for 5 months. The tumor grew well only in intact males; it grew moderately well in intact females and did not grow in castrates. The metabolism of testosterone-3H by this tumor was studied by injecting 0.5 mCi of the labeled steroid (specific activity, 45 Ci/mmole) into tumor-bearing males 1 hr before decapitation. Samples of tumor tissue, liver, muscle, and prostate were obtained and the distribution of radioactive metabolites of testosterone-3H was analyzed by thin-layer chromatography. 5α-Dihydrotestosterone and 3α-androstandiol were the major metabolites found in both the tumor and the prostate. These metabolites were absent or were found in smaller amounts in the nontarget tissues, liver and muscle. The preferred metabolism of testosterone via 5α-reduction, together with the better growth of the tumor in intact males, indicates that this is an androgen-responsive tumor.