Counteraction of underfeeding-induced inhibition of mammary tumor growth in rats by prolactin and estrogen administration

The purpose of this study was to determine whether administration of estrogen or/and haloperidol (HAL), a drug that increases prolactin (PRL) secretion, could counteract the inhibitory effects of underfeeding on growth of established carcinogen-induced mammary cancers in rats. Sprague-Dawley female rats were fed half of the complete diet consumed daily by ad libitum fed controls, beginning 1 week before daily injection of estradiol benzoate (EB) or/and HAL for 3 weeks. Body weight, mammary tumor number, and mammary tumor diameter were measured at weekly intervals, and at the end of the 3 weeks blood was collected for assay of serum PRL. Full-fed (FF) control rats showed an increase by the end of 3 weeks in average body weight, mammary tumor number, and mammary tumor size whereas half-fed (HF) rats showed a significant decrease in average body weight, tumor number, and tumor size, and serum PRL concentrations when compared with these parameters in FF rats. Administration of EB to the HF rats partially prevented loss of mammary tumor size and significantly increased serum PRL levels over those of HF or FF control rats. Injection of HAL or the combination of HAL and EB completely prevented the decrease in mammary tumor number and size in the HF rats. These results suggest that regression in number and size of established mammary tumors in HF rats during a 3-week period is due primarily to a decrease in secretion of estrogen and PRL, the two hormones essential for mammary tumor growth in rats.link_to_subscribed_fulltex

Inhibition of mammary tumor growth by dexamethasone in rats in the presence of high serum prolactin levels

Female Sprague-Dawley rats with established 7,12-dimethylbenz(a)anthracene-induced mammary tumors were given daily s.c. injections of 50 μg dexamethasone per rat, 0.5 mg haloperidol per kg, or both for 3 weeks. Control rats received the injection vehicles only. Mammary tumor growth was measured at weekly intervals for 21 days, and blood was collected on Days 10 and 21 of treatment for assay of prolactin. Dexamethasone produced significant regression of mammary tumors and reduced serum prolactin levels, whereas haloperidol significantly increased mammary tumor growth and greatly elevated serum prolactin levels. When dexamethasone and haloperidol were injected together, there was significant regression of mammary tumors despite markedly elevated serum prolactin levels. No significant differences in specific prolactin binding to membrane preparations of mammary tumors from these animals were observed in any treatment group. These results indicate that dexamethasone, a synthetic gluco-corticoid, can directly inhibit mammary tumor growth in the presence of elevated serum prolactin levels produced by haloperidol, and the inhibition is not due to a reduction of prolactin binding sites in the tumor tissue.link_to_subscribed_fulltex