METABOLISM OF ESTRADIOL AND ESTRONE IN ORGAN-CULTURES OF DORSOLATERAL AND VENTRAL PROSTATE OF UNTREATED AND SEX-HORMONE IMPLANTED RATS

Since dorsolateral but not ventral prostate undergoes estrogen-induced dysplasia in the androgen-supported Noble rat in 16 weeks, we studied estrogen metabolism by these tissues from untreated and sex hormone-implanted animals. We incubated 8.5 nM [6,7-H-3]-labeled estradiol (E2) and estrone (E1) for 21 hours in serum-free, prostate-lobe cultures and 8.5 nM [2-H-3]E2 with explants from untreated rats and animals treated with testosterone, 5-alpha-dihydrotestosterone, or E2 plus testosterone. Untreated rat ventral prostate metabolized 3.7 times as much E2 to E1 as dorsolateral prostate, whereas the latter tissue converted 2.5 times as much E1 to E2 as the former. After dorsolateral prostate culture with 8.5 nM [6,7-H-3]-labeled E2 or E1, 0.6 M KCl-extracted, Sephadex G25-excluded nuclear protein bound preponderantly E2, whereas the counterpart nuclear protein fraction from ventral prostate explants incubated with E2 bound substrate and E1 almost equally. The combination sex hormone treatment decreased E2 metabolism and increased its uptake by the dysplastic dorsolateral prostate. Implantation of 5-alpha-dihydrotestosterone, but not of testosterone, also decreased E2 metabolism to E1 by dorsolateral prostate cultures. Treatments with E2 plus testosterone and with 5-alpha-dihydrotestosterone changed E2 uptake/E1 retention in dorsolateral prostate explants from 2.4 to 7.4 and 8.5, respectively. C-2 tritium release marking the 2,3-catechol estrogen pathway was greater for ventral than dorsolateral prostate, but was unaffected by the sex hormone treatments. Nuclear ligand preponderance of E2 could account for the reported presence of type II estrogen-binding sites in the rat dorsolateral prostate and help to explain induction of lobe-specific dysplasia and adenocarcinoma after chronic androgen/estrogen combination treatment.