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Stimulation of Growth of Carcinogen-induced Mammary Cancers in Rats by Thyrotropin-releasing Hormone¹

Department of Physiology, Neuroendocrine Research Laboratory, Michigan State University, East Lansing, Michigan 48824

Twice-daily injections of three different doses of synthetic thyrotropin-releasing hormone (TRH), a hormone normally produced by the hypothalamus, produced significant increases in size and number of 7,12-dimethylbenz(a)anthracene-induced mammary cancers over 0.87% NaCl solution-injected control rats. When thyroidectomized rats, bearing 7,12-dimethylbenz(a)anthracene-induced mammary tumors were given the same twice-daily injections of TRH, mammary tumor growth was increased to the same extent as in intact rats given TRH, showing that the effects of TRH were not exerted via stimulation of thyroid function. The TRH-induced increments in mammary tumor growth were accompanied by significant increases in serum prolactin levels over 0.87% NaCl solution-injected controls. A single daily injection of 2-bromo--ergocryptine (CB-154), a prolactin-release inhibitor, completely blocked TRH-induced mammary tumor growth and reduced serum prolactin values. These results indicate that a twice-daily pulse of TRH can stimulate mammary tumor growth by releasing prolactin from the anterior pituitary.

¹ Supported in part by NIH Research Grant CA 10771 from the National Cancer Institute and Grant AM 04784 from the National Institute for Arthritis, Metabolism and Digestive Diseases.

² Present address: Mount Sinal Hospital, 600 University Avenue, Toronto, Ontario, Canada MSG 1X5.

³ To whom requests for reprints should be addressed.

Received 7/26/76. Accepted 10/ 7/76.