Antiestrogens do not counteract the inhibitory effect of estradiol-17 beta on the growth of the Dunning R3327 prostatic adenocarcinoma.
The purpose of this study was to investigate if the local effects of estradiol on the Dunning R3327 prostatic adenocarcinoma were estrogen-receptor mediated. All rats with the transplantable Dunning R3327 prostatic adenocarcinoma were castrated on the first day of treatment and were supplemented with daily s.c. injections of testosterone propionate (0.1 mg) during the treatment period, lasting for 6 weeks. The following treatment groups were studied: castration + testosterone supplementation (C + T, control group), C + T and estradiol-17 beta (50 micrograms/daily s.c.), C + T and tamoxifen (1 mg twice a week s.c.), and C + T and estradiol-17 beta in combination with tamoxifen. Tumor volumes were measured every week. At the end of the treatment period, pieces of the tumors were taken for morphological studies and estrogen-receptor analysis. In the groups of rats given tamoxifen treatment no estrogen-receptor binding was detectable in prostatic tumors, but, despite this, tamoxifen did not prevent either the inhibitory effect of estradiol-17 beta on the tumor growth rate or the estrogen-induced decrease of volume density of prostatic glandular epithelium. In contrast, the estrogen-induced increase of volume density of the stroma was abolished by tamoxifen, suggesting that this effect may be mediated by the estrogen receptor. A morphometrical method for estimating the growth of different tumor compartments is presented. Treatment with estradiol-17 beta, both with or without combined treatment with tamoxifen, reduced the growth of both the tumor epithelium and stroma. The direct effect of estradiol-17 beta on the growth and morphology of the Dunning R3327 prostatic adenocarcinoma seemed not to be mediated by the estrogen receptor.
Landström
M
M
Department of Physiology, University of Umeå, Sweden.
Damber
J E
JE
Bergh
A
A
Tomic
R
R
Carlsson-Bostedt
L
L
Stigbrand
T
T
D000230:Adenocarcinoma / Q000032:analysis / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000627:therapeutic use*; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D008297:Male; D009368:Neoplasm Transplantation; D009919:Orchiectomy; D011257:Pregnancy Proteins / Q000032:analysis; D011471:Prostatic Neoplasms / Q000032:analysis / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D011960:Receptors, Estrogen / Q000032:analysis / Q000187:drug effects; D013629:Tamoxifen / Q000627:therapeutic use; D013739:Testosterone / Q000008:administration & dosage; D013997:Time Factors
D004965:Estrogen Antagonists; D011257:Pregnancy Proteins; D011960:Receptors, Estrogen; C033484:pregnancy-associated murine protein 1; D013629:Tamoxifen; D013739:Testosterone; D004958:Estradiol