Composite (Plastic) Fillings U-Shaped Curve
Prostate enlargement in mice due to fetal exposure to low doses of
estradiol or diethylstilbestrol and opposite effects at high doses
Frederick S. vom Saal, Barry G. Timms, Monica M. Montano, Paola
Palanza, Kristina A. Thayer, Susan C. Nagel, Minati D. Dhar, V.K.
Ganjam, Stefano Parmigiani, and Wade V. Welshons
Proceedings of the National Academy of Sciences, Volume 94, page
2056-2061, March 1997
Abstract
On the basis of results of studies using high doses of estrogens,
exposure to estrogen during fetal life is known to inhibit prostate
development. However, it is recognized in endocrinology that low
concentrations 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 number of prostatic androgen
receptors per cell was permanently increased by 2-fold, and the
prostate was enlarged by 30% (due to hyperplasia) relative to
untreated males. However, as the free serum estradiol concentration
weight decreased relative to males exposed to the 50% increase in
estradiol. As a model for fetal exposure to man-made estrogens,
pregnant 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 doses decreased adult prostate weight in male
offspring. Our findings suggest that a small increase in estrogen may
modulate the action of androgen in regulating prostate
differentiation, resulting in a permanent increase in prostatic
androgen receptors and prostate size. For both estradiol and DES,
prostate weight first increased then decreased with dose, resulting
in an inverted-U dose-response relationship.