Counteraction by Prolactin of Androgen-Induced Inhibition of Mammary Tumor Growth in Rats

Summary

We investigated whether growth of 7,12dimethylbenz[a]anthracene-induced mammary adenocarcinomas, inhibited by an androgen, dromostanolone propionate, could be overcome by daily injections of prolactin. Female Sprague-Dawley rats with established mammary tumors were injected subcutaneously (sc) daily for 3 weeks with corn oil (controls), 0.5 mg dromostanolone propionate (DP) in corn oil, 1.0 mg NIH ovine prolactin, or 0.5 mg DP and 1.0 mg prolactin. Mammary tumors in control rats showed an increase in mean tumor diameter (MTD) by 48.4% and in mean tumor number (MTN) by 66.5% by the end of the treatment period, whereas DP produced a decrease of 65.6% in total MTD and 60.6% in MTN/rat. Prolactin alone produced gains of 169.8% in total MTD and 248.2% in MTD/rat. Simultaneous treatment with DP and prolactin cempletely prevented mammary tumor inhibition and moderately increased MTD and MTN. Termination of treatment resulted in continued tumor growth in controls, only slight resumption of tumor growth in the previously DP-treated rats, regression of tumor size and number in rats previously given prolactin alone, and a reduction in tumor growth in rats given both DP and prolactin. These results indicate that DP exerts its antitumor effects by blocking the peripheral stimulatory action of prolactin on the mammary tumor tissue, and that exogenously administered prolactin can overcome this inhibitory action of DP.