Because mammary glands are surrounded by adipose tissues, we hypothesize that the ultra-lipophilic endogenous estrogen-17beta-fatty
acid esters may have preferential hormonal and carcinogenic effects in mammary tissues compared to other target organs (such as the uterus and pituitary). This hypothesis is tested in the present study. We found that all 46 rats implanted with an
estradiol-17beta pellet developed large
pituitary tumors (average weight=251+/-103 mg) and had to be terminated early, but only 48% of them developed mammary
tumors. In addition, approximately one-fourth of them developed a huge uterus. In the 26 animals implanted with a mixture containing
estradiol-17beta-stearate and
estradiol-17beta-palmitate (two representative
estradiol-17beta-
fatty acid esters) or in the 29 animals implanted with
estradiol-17beta-stearate alone (in the same molar dose as
estradiol-17beta), 73% and 79%, respectively, of them developed mammary
tumors, whereas only 3 or 2 animals, respectively, had to be terminated early due to the presence of a large
pituitary tumor. Both tumorous and normal mammary tissues contained much higher levels of
estrogen esterase than other tissues, which catalyzes the releases of bioactive
estrogens from their
fatty acid esters. In conclusion, while
estradiol-17beta is much stronger in inducing
pituitary tumor (100% incidence) than mammary
tumor, estradiol-17beta-fatty
acid esters have a higher efficacy than
estradiol-17beta in inducing mammary
tumor and yet it only has little ability to induce uterine out-growth and pituitary
tumorigenesis. This study establishes the endogenous estrogen-17beta-fatty
acid esters as preferential inducers of mammary
tumorigenesis.