Neonatal low- and high-dose exposure to estradiol benzoate in the male rat: I. Effects on the prostate gland

Brief exposure of rats to high doses of natural estrogens early in life res ults in permanent alterations of the prostate gland, which include differen tiation defects, altered gene expression, and dysplasia with aging. Whether low-dose treatments can cause similar effects in the developing prostate r emains controversial. The current project was designed to determine the dos e-response relationship of the prostate gland to estradiol exposure during the developmentally critical neonatal period in the rat. Male Sprague-Dawle y (SD) rats were treated on Days 1, 3, and 5 of life by s.c. injections of a 7-log range of doses (0.015 mug/kg to 15.0 mg/kg) of beta -estradiol-3-be nzoate (EB) in 25 mul of peanut oil (Arachis) as vehicle. In a separate blo ck, neonatal Fisher 344 (F344) rats received 0.15, 15.0, or 1500.0 mug EB/k g. Rats were killed on Postnatal Day (PND) 35 or 90, and the prostates were microdissected, weighed, and frozen for immunohistochemistry. Preputial se paration and hepatic testosterone hydroxlase activities were monitored and measured to determine the onset of puberty. On PND 35, there was an increas e in prostate weights of SD rats treated with low doses of EB and a decreas e in prostate weights of SD rats treated with high doses. The low-dose effe ct was entirely abolished by PND 90, and only high-dose suppression of orga n sizes was found. The transient nature of the effect in low-dose animals s uggests an advancement of puberty as the cause for increased reproductive o rgan weights on PND 35. F344 rats were more sensitive than SD rats to the s uppressive effects of high doses of neonatal EB on PND 90. Despite this hei ghtened responsiveness in the F344 rats, a low-dose estrogenic effect on ad ult prostate weights was not observed. Thus, in the rat model a sustained e ffect at low doses of natural estrogens is not present in the prostate glan ds.