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Hormone Sensitivity of the R3327-G Rat Prostate Adenocarcinoma: Growth Rate, DNA Content, and Hormone Receptors¹

Surgical Service [A. P., G. L. I., N. L. B., R. M. L.], Veterans Administration Medical Center, Miami, Florida 33125, and Departments of Surgery [A. P., G. L. I., A. J. C.] and Urology [N. L. B., B. J. S.], University of Miami School of Medicine, Miami, Florida 33101

The growth of the R3327-G rat prostatic adenocarcinoma was significantly reduced when implanted in orchiectomized male rats (ORCH tumors). Tumors grown in intact animals (control tumors) had a doubling time of 7.4 days as compared to 9.2 days in ORCH tumors. A computer-based analysis of flow cytometric DNA histograms also detected significant differences between control and ORCH tumors. ORCH tumors were found to have 25% fewer cells with hyperdiploid DNA than control tumors (p < 0.01). This androgen sensitivity in growth rate and the proportion of hyperdiploid cells were further reflected in the binding of [³H]methyltrienolone ([³H]R1881) to cytoplasmic (cytosol) and nuclear tumor extracts. ORCH tumor cytosols had a [³H]R1881 binding capacity which was 70% lower than controls (6071 fmol/g tumor tissue). Nuclear [³H]R1881 binding in ORCH tumors was undetectable in seven of eight samples while in control tumors, binding was detectable in five of six preparations. Sucrose density gradient analysis showed that cytosolic [³H]R1881 receptors sedimented at 8.1S in low salt and 4.6 to 3.3S in high salt. Nuclear [³H]R1881 receptors in high salt sedimented at 4.1 to 3.3S. Competition experiments using [³H]R1881 showed that [³H]R1881 receptors were primarily androgenic, although some displacement by estradiol did occur. In contrast, [³H]estradiol binding was found to be highly specific. The binding capacity of [³H]estradiol in ORCH tumor cytosols was 30% higher than controls (962 fmol/g tumor issue), while binding to ORCH and control nuclear extracts was similar. These data suggest that the inhibition of androgen-sensitive R3327-G tumor cells was related to the concentration of androgen receptors and that this in turn was expressed as a reduction in the proportion of hyperdiploid cells.

¹ Supported in part by Veteran Administration Medical Center Grant 4321001; Coulter Electronics, Hialeah, Fla.; Surgical Scholarship Fund, University of Miami School of Medicine, Miami, Fla.; Weeks Endowment Fund; Urology Research Fund, Inc.; and NIH Grant 5R26CA2169603.

² To whom requests for reprints should be addressed, at Research Service 151, Veterans Administration Medical Center, 1201 N.W. 16th Street, Miami, Fla. 33125.

Received 5/19/81. Accepted 3/ 8/82.