Preferential growth stimulation of mammary glands over uterine endometriumin female rats by a naturally occurring estradiol-17 beta-fatty acid ester

We hypothesize that the endogenously present lipoidal estrogen fatty, acid esters may have a stronger mitogenic action in the fat-rich mammary tissues than in the uterus. To test this hypothesis, we compared the activity of e stradiol-17 beta -stearate (E-2-17 beta -S) with that of estradiol-17 beta (E-2) in stimulating the growth of mammary glandular cells versus the growt h of uterine endometrial cells in ovariectomized female Sprague Dawley rats . Experimentally, an estimated 0.5 or 5 nmol of E-2-17 beta -S or E-2 was r eleased daily to ovariectomized female rats through an Alzet pump implanted under the back skin of the animal for 10 or 23 days. The growth-stimulator y effect of E-2-17 beta -S and E-2 on mammary glandular cells was determine d according to 5-bromo-2 ' -deoxyuridine labeling indices, and their effect on the uterus was determined by measuring both the 5-bromo-2 ' -deoxyuridi ne labeling index and the uterine wet weight. Our results showed that chron ic treatment of ovariectomized female rats with 0.5 or 5 nmol/day E-2-17 be ta -S for 10 or 23 days had a stronger stimulatory effect on mammary glandu lar cell proliferation than treatment with equimolar doses of E-2- In the u terus, however, E-2 was more active in stimulating the proliferation of ute rine endometrial cells than E-2-17 beta -S at equimolar doses. Our results demonstrated, for the first time, that a naturally occurring estradiol-17 b eta -fatty acid ester has a differential, strong mitogenic effect in the fa t-rich mammary tissues, and this effect was not observed with E-2. It is te mpting to suggest that the fatty acid esters of the endogenous estrogens an d their bioactive metabolites (e.g., 4-hydroxyestradiol and 16 alpha -hydro xyestrone) may be of unique importance for stimulating cell growth and poss ibly also for inducing tumor formation in the fat-rich mammary tissues as c ompared with the uterus. More studies are warranted to test these ideas.