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NEONATAL LOW- AND HIGH-DOSE EXPOSURE TO ESTRADIOL BENZOATE IN THE MALE RAT: I. EFFECTS ON THE PROSTATE GLAND
Putz, O., C. B. Schwartz, S. Kim, G. A. LaBlanc, R L. Cooper, AND G. Prins. NEONATAL LOW- AND HIGH-DOSE EXPOSURE TO ESTRADIOL BENZOATE IN THE MALE RAT: I. EFFECTS ON THE PROSTATE GLAND. BIOLOGY OF REPRODUCTION 65(5):1496-1505, (2001).
Neonatal Low- And High-Dose Exposure To Estradiol Benzoate In The Male Rat: 1. Effects On The Prostate Gland. Oliver Putz, Christian B. Schwartz, Steve Kim, Gerald A. LeBlanc Ralph L. Cooper, Gail S. Prins
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 with a 7-log range of doses (0.015 g/kg to 15.0 mg/kg) of -estradiol-3-benzoate (EB) by subcutaneous injections in 25 l of peanut-oil (Arachis) as vehicle. In a separate block, neonatal Fisher 344 (F344) rats received 0.15, 15.0 or 1500.0 g EB/kg. Rats were sacrificed on postnatal days (PND) 35 or 90, the prostates were micro-dissected, weighed and frozen for immunohistochemistry. Additionally, pubertal markers were monitored and measured. On PND 35, we observed an increase in prostate weights of SD rats treated with low doses of EB, while high doses reduced organ weights. The low-dose effect was entirely abolished on PND 90, and only high-dose suppression of organ sizes was found. The transient nature of the effect in low-dosed animals suggests an advancement of puberty as the cause for increased reproductive organ weights on PND 35. F344 rats exhibited an increased sensitivity to the suppressive effects of high doses of neonatal EB when compared to SD rats on PND 90. Despite this heightened responsiveness in the F344 rats, a low-dose estrogenic effect on adult prostate weights was not observed. We thus conclude that in the rat model, a sustained effect at low doses of natural estrogens is not present in the prostate glands.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
REPRODUCTIVE TOXICOLOGY DIVISION