Influence of thyroidectomy and prolactin suppression on the growth of N-nitrosomethylurea-induced rat mammary carcinomas.

Mammary carcinomas were induced in female Sprague-Dawley rats with N-nitrosomethylurea. Thyroidectomy increased the serum prolactin and reduced serum growth hormone levels of 17 rats without affecting tumor growth. Pergolide mesylate, 80 micrograms twice daily for 7 days, suppressed the serum prolactin of another 17 animals; seven of 17 tumors continued to grow, four became static, and six (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 ten of the 14 tumors (71%), while two became static, and two continued to grow. Five of the ten regressions were complete. Only the combined thyroidectomy-pergolide treatment group showed a significant difference in posttreatment surface area compared with the controls (p less than 0.001). Ovine growth hormone, 40 micrograms/hr delivered by s.c. osmotic minipumps for 7 days, stimulated regrowth of six of seven tumors undergoing regression in response to thyroidectomy plus pergolide; the other one became static. Thyroxine, 2 micrograms/100 g body weight, stimulated regrowth of the tumors in another six 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.