PROSTATE ENLARGEMENT IN MICE DUE TO FETAL EXPOSURE TO LOW-DOSES OF ESTRADIOL OR DIETHYLSTILBESTROL AND OPPOSITE EFFECTS AT HIGH-DOSES

On the basis of results of studies using high doses of estrogens, expo sure to estrogen during fetal life is known to inhibit prostate develo pment, However, it is recognized in endocrinology that low concentrati ons of a hormone can stimulate a tissue, while high concentrations can have the opposite effect, We report here that a 50% increase in free serum estradiol in male mouse fetuses (released by a maternal Silastic estradiol implant) induced a 40% increase in the number of developing prostatic glands during fetal life; subsequently, in adulthood, the n umber of prostatic androgen receptors per cell was permanently increas ed by 2-fold, and the prostate was enlarged by 30% (due to hyperplasia ) relative to untreated males, However, as the free serum estradiol co ncentration in male fetuses was increased from 2- to 8-fold, adult pro state weight decreased relative to males exposed to the 50% increase i n estradiol, As a model for fetal exposure to man-made estrogens, preg nant mice were fed diethylstilbestrol (DES) from gestation days 11 to 17, Relative to controls, DES doses of 0.02, 0.2, and 2.0 ng per g of body weight per day increased adult prostate weight, whereas a 200-ng- per-g dose decreased adult prostate weight in male offspring, Our find ings suggest that a small increase in estrogen may modulate the action of androgen in regulating prostate differentiation, resulting in a pe rmanent increase in prostatic androgen receptors and prostate size, Fo r both estradiol and DES, prostate weight first increased then decreas ed with dose, resulting in an inverted-U dose-response relationship.