UNDERFEEDING-INDUCED SUPPRESSION OF MAMMARY-TUMORS - COUNTERACTION BYESTROGEN AND HALOPERIDOL

The purpose of this study was to investigate the mechanism by which un derfeeding induces regression of carcinogen-induced mammary tumors in the rat and to determine if tumor regression in underfed rats could be prevented on a chronic basis by maintaining elevated circulating leve ls of estrogen and/or prolactin (PRL) by treatment with estradiol benz oate (EB) and a dopamine receptor blocker, haloperidol (HAL). Female r ats with 7,12-dimethylbenzanthracene-induced mammary tumors were fed a d libitum (full-fed), half-fed (HF), or half-fed and treated with EB ( HF+EB), HAL (HF+HAL), or both (HF+EB+HAL) for 15 weeks. Tumor diameter , tumor number, and body weight were determined each week. At the end of the experiment, hypothalamic concentrations of catecholamines, indo leamines, and their metabolites were determined by high performance li quid chromatography. Tumor diameter, tumor number, and body weight inc reased progressively in the full-fed rats, but decreased significantly in the HF rats. Treatment of HF rats with EB, HAL, or both prevented tumor regression, but had no effect on body weight, which declined con tinuously. In the HF rats, there was an increase in the concentration of dopamine and a decrease in the concentration of serotonin in the hy pothalamus, whereas treatment with HAL reversed these effects. EB had no effect on neurotransmitter concentrations in the HF rats, but treat ment of HF+EB animals with HAL decreased the dopamine concentration. T he changes in dopamine and serotonin observed in HF rats are known to inhibit PRL secretion, whereas HAL, which blocked these changes, is a well established stimulator of PRL secretion. Since the mammary tumors are dependent on PRL for development and growth, it is probable that the regression of these tumors in the HF rats was ultimately due to a decrease in PRL secretion, and the prevention of this regression in HF +HAL rats was ultimately due to an increase in PRL secretion. EB, a po tent PRL stimulator, probably blocked tumor regression in HF+EB rats b y increasing PRL secretion by a direct effect on the pituitary.