Our objective is to establish whether endocrine factors, specifically estradiol and its mode of metabolism and plasma prolactin, are related to the initiation and/or promotion of a mammary tumorigenesis in female rats on varying types and amounts of dietary fat. Catechol estrogens are significant metabolites of estrogens in humans and animals. They are considered by some investigators to be regulatory factors in the central nervous system for gonadotropin and prolactin secretion and also as """"""""impeding"""""""" estrogens. In addition, in situations of equivalent estradiol secretions, a metabolic preference for the pathway leading to the synthesis of catechol estrogens or estriol may cause a hypo- or hyperestrogenic state, respectively. Similarly, the prolactin estrogen ratio has been implicated in the breast tumor process. To this end, plasma estrone, 2-hydroxyestrone, estradiol, prolactin and the fecal and urinary excretions of catechol estrogens (2-hydroxyestrone, 2-hydroxyestradiol) and estriol will be measured in female Sprague-Dawley rats on semisynthetic diet containing 5, 10 and 20% polyunsaturated (safflower oil) or saturated (coconut oil) fat starting at the age of 22 days (immature) or 50 days. Further, in similar groups of rats, the tumor will be induced by 7, 12-dimethylbenzanthracene (DMBA). Sites, times of appearance and size of tumors will be correlated with prolactin and the amounts of nature of estradiol and its metabolites. The mode of metabolism will further be investigated by radiometric analysis and by isolation, identification and measurements of radioactive metabolites in the urine and feces.
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