Subcellular distribution in vivo of testosterone and salt extractability of nuclear androgen complexes in the prostate and prostatic adenocarcinoma: effect of estrogen treatment
Batra, S.; Wännman, H.; Alenfall, J.; Forsgren, B.
In Vivo 6(6): 573-578
1992
ISSN/ISBN: 0258-851X PMID: 1296804 Document Number: 396840
The distribution of injected (3H)testosterone into nuclear (Nt) mitochondrial-microsomal (Mp) and cytosolic fractions (Cs) obtained from hormone-dependent R-3327 Dunning tumor, dorsal prostate, ventral prostate and heart ventricle, as a non-target tissue, was studied. Since it has been suggested that salt resistant steroid receptor complexes may represent acceptor sites, extractability of nuclear androgen complexes with high KCl (0.6 M) solution was also determined. Both orchiectomized (Or) and estrogen treated (E-2) rats were used. The distribution of bound radioactivity between Nt and Cs fractions was very similar in tumors, dorsal and ventral prostate, being approximately 50% and 10% in Nt and Cs, respectively. In heart the corresponding figures were 15% and 12%, respectively. The concentration of radioactivity/mg protein in a nuclear KCl-extract (Ne) from tumors was approximately 10-fold higher than that in the salt-resistant (Nr) fraction and also nearly 10-fold higher than that in Cs. Similar distribution patterns were observed in dorsal and in ventral prostate, but the concentration in Ne from ventral prostate was higher than that from tumors or dorsal prostate. Both total and bound radioactivity in Cs from heart was similar to that in the tumors, whereas the concentration in Ne from heart was lt 2% of that in Ne from tumors. No significant differences were found in the distribution of radioactivity in tumors or tissues obtained from Or or E-2 rats. These data show that a very large portion of the injected testosterone is bound to Ne in the target tissues, and that there was no difference in the concentration in Cs from target and non-target tissue, which supports the single-step model for the mechanism of action of sex steroids. Estrogen treatment does not change the availability or subcellular distribution of (3H)testosterone in tumor or prostate.