Estradiol binding in ovariectomy-responsive and -nonresponsive rat mammary carcinoma

MTW9, a transplantable mammary tumor in Wistar-Furth rats, is dependent upon high levels of serum prolactin for growth. The mammary tumor can be maintained by coimplantation with a pituitary mammosomatotropic tumor (MTW9-MtT) or by chronic perphenazine administration (MTW9-P). MTW9-MtT does not regress after ovariectomy (OVEX) alone, while, MTW9-P regresses rapidly whether or not rats are maintained on perphenazine. Cytosol estradiol binding was determined in MTW9-MtT, 47.6 +/- 3.6 (N = 9), Kd 9.9 +/- 2.0 X 10(-11) M; MTW9-P, 195.5 +/- 9.1 (n = 16), Kd 27.6 +/- 4.7 X 10(-11) M; MTW9-P after perphenazine was withdrawn, 86.0 +/- 6.0 (n = 6), Kd 9.9 +/- 1.5 X 10(-11) M. Eight S and 4 S peaks were found in cytosols from both tumors by sucrose gradient centrifugation; the peaks differ qualitatively and quantitatively. The possibility that differences in binding levels result from sites filled with endogenous estradiol was critically examined and rejected. Withdrawal of perphenazine results in reduction of estradiol binding but retention of response to OVEX. Hence, response of MTW9-P to OVEX cannot be explained by the 3- to 4-fold increase in estradiol binding over MTW9-MtT. The relationship between estradiol binding and response to OVEX is under study using both mammary tumor models.