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Regular Article |
a Department of Urology (M/C 955), College of Medicine, University of Illinois, Chicago, Illinois 60612-7310
b Department of Environmental & Molecular Toxicology, North Carolina State University, Raleigh, North Carolina 27695-7633
c Endocrinology Branch, Reproductive Toxicology Division, National Health and Environment Effects Research Laboratory MD72, United States Environmental Protection Agency, Durham, North Carolina 27713
ABSTRACT
Brief exposure of rats to high doses of natural estrogens early in life results in permanent alterations of the prostate gland, which include differentiation defects, altered gene expression, and dysplasia with aging. Whether low-dose treatments can cause similar effects in the developing prostate remains controversial. The current project was designed to determine the dose-response relationship of the prostate gland to estradiol exposure during the developmentally critical neonatal period in the rat. Male Sprague-Dawley (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 µg/kg to 15.0 mg/kg) of ß-estradiol-3-benzoate (EB) in 25 µl of peanut oil (Arachis) as vehicle. In a separate block, neonatal Fisher 344 (F344) rats received 0.15, 15.0, or 1500.0 µg EB/kg. Rats were killed on Postnatal Day (PND) 35 or 90, and the prostates were microdissected, weighed, and frozen for immunohistochemistry. Preputial separation and hepatic testosterone hydroxlase activities were monitored and measured to determine the onset of puberty. On PND 35, there was an increase in prostate weights of SD rats treated with low doses of EB and a decrease in prostate weights of SD rats treated with high doses. The low-dose effect was entirely abolished by PND 90, and only high-dose suppression of organ sizes was found. The transient nature of the effect in low-dose animals suggests an advancement of puberty as the cause for increased reproductive organ weights on PND 35. F344 rats were more sensitive than SD rats to the suppressive effects of high doses of neonatal EB on PND 90. Despite this heightened responsiveness in the F344 rats, a low-dose estrogenic effect on adult prostate weights was not observed. Thus, in the rat model a sustained effect at low doses of natural estrogens is not present in the prostate glands.
1 Supported by EPA STAR grant R826299 to G.S.P.
2 Correspondence: Gail S. Prins, Department of Urology (M/C 955), University of Illinois, 820 South Wood Street, Chicago, IL 60612-7310. FAX: 312 996 1291; gprins{at}uic.edu
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