Inhibition by neonatal hypothalamic estrogen implantation of carcinogen-induced mammary tumorigenesis in female rats
Hayashi, S.; Nagasawa, H.
Gan 68(2): 139-143
1977
ISSN/ISBN: 0016-450X PMID: 408212 Document Number: 117154
The relationship between neonatal treatment with estrogen and induction of mammary tumors by 7,12-dimethylbenzanthracene (DMBA) in female rats was examined. Five day old female rats received intrahypothalamic implantation of micropellets of 0.4 .mu.g of estradiol-paraffin mixture or paraffin vehicle only (sham operated control), or no operation (intact control). Induction of mammary tumor in these rats was examined after DMBA was given at 45 days of age intragastrically. The rats bearing the micropellets of the estradiol-paraffin mixture in the anterior to middle part of the hypothalamus showed persistent vaginal estrus while rats bearing the same pellets in the middle to posterior part of the hypothalamus showed regular cyclic changes in daily vaginal smears. Compared to intact or sham operated controls, mammary tumor appearance was delayed in rats which received 0.4 .mu.g of estradiol intrahypothalamically and showed persistent vaginal estrus (10 wk vs. 15 wk after DMBA administration, respectively). Since the vagina of rats with intrahypothalamic micropellets of estradiol-paraffin mixture opened at the same age as intact or sham operated controls and the mammary rating of the former rats was the same as the latter, it can be concluded that the hypothalamus of the former rats was changed by the steroid while the neonatal mammary glands received little effect. The delay or suppression of mammary tumorigenesis in DMBA-treated rats by neonatal steroid administration is attributable to irreversible changes in the hypothalamo-pituitary-gonadal axis.