INFLUENCE OF THYROIDECTOMY AND PROLACTIN SUPPRESSION ON THE GROWTH OF N-NITROSOMETHYLUREA-INDUCED RAT MAMMARY CARCINOMAS

Abstract

Mammary carcinomas were induced in female Sprague-Dawley rats with N-nitromethylurea. Thyroidectomy increased the serum prolactin and reduced serum growth hormone levels of 17 rats without affecting tumor growth. Pergolide mesylate, 80 .mu.g twice daily for 7 days, suppressed the serum prolactin of another 17 animals; 7 of 17 tumors continued to grow, 4 became static and 6 (35%) underwent partial regression. Treatment with pergolide mesylate plus thyroidectomy reduced both serum prolactin and growth hormone in all of 14 rats, caused regression of 10 of the 14 tumors (71%), while 2 became static, and 2 continued to grow. Five of the 10 reressions were complete. Only the combined thyroidectomy-pergolide treatment group showed a significant difference in posttreatment surface area compared with the controls (P < 0.001). Ovine growth hormone, 40 .mu.g/h delivered by s.c. osmotic minipumps for 7 days, stimulated regrowth of 6 of 7 tumors undergoing regression in response to thyroidectomy plus pergolide; the other one became static. Thyroxine, 2 .mu.g/100 g body wt, stimulated regrowth of the tumors in another 6 thyroidectomized rats despite continued suppression of prolactin by pergolide. Thus, regression of N-nitrosomethylurea-induced mammary tumors produced by thyroidectomy plus pergolide is due to the combined suppression of circulating growth hormone and prolactin.