Perinatal exposure to estrogenic compounds and the subsequent effects on the prostate of the adult rat: evaluation of inflammation in the ventral and lateral lobes.
Although the effects of estrogenic compounds administered during the perinatal period on the size and morphology of the prostate have been well documented, the effects of such exposures on inflammatory changes in the prostate have not been well characterized. Since neonatal estradiol exposure has been shown to cause periods of hyperprolactinemia later in life and a relationship exists between high prolactin levels and rat lateral prostate inflammation, we hypothesized that an exposure to environmental compounds with estrogenic activity could result in an increase in lateral prostate inflammation in adulthood. To investigate this possibility and compare differences between estrogen agonists and antagonists, we examined the effect of a perinatal exposure to 17beta-estradiol, the insecticide methoxychlor, the partial estrogen agonist tamoxifen, and the pure antiestrogen ICI 182,780. Dams were dosed from gestation day (GD)18 to parturition and then the pups were dosed from postnatal day (PND) 1 to 5 with 0.1 mL of a solution of 0.355 mM and .0178 mM by sc injection, respectively, of all compounds in sesame oil, except for methoxychlor, which was administered only to the dam by gavage from GD 18 through PND 5 at a dose of 50 mg/kg in sesame oil. At 90 d of age, the weight of the lateral and ventral prostate in the estradiol group was significantly decreased. Tamoxifen caused a decrease in the weight of the lateral prostate, whereas the ventral lobe was not affected. ICI 182,780 did not alter prostate weight. The methoxychlor exposure increased the lateral lobe weight, but the ventral lobe weight was not affected. In the estradiol and tamoxifen groups, an inflammatory infiltrate was observed in the ventral prostates in 45.0 and 27.8% of the animals, respectively. There was a significant increase in the percent and severity of inflammation in the lateral prostate (as determined by a myeloperoxidase or neutrophil quantification assay) in the estradiol, tamoxifen, and methoxychlor groups as compared to controls. The ICI group was comparable to the controls in both ventral and lateral lobes. This study demonstrates that perinatal exposure to estrogenic compounds can result in alterations in the size of the adult prostate and increase the incidence of prostatitis.
Stoker
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Endocrinology Branch, Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, USA. stoker.tammy@epa.gov
Robinette
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Cooper
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D000375:Aging / Q000187:drug effects; D000818:Animals; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology / Q000633:toxicity*; D004965:Estrogen Antagonists / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D000077267:Fulvestrant; D007306:Insecticides / Q000378:metabolism / Q000633:toxicity; D008297:Male; D008731:Methoxychlor / Q000378:metabolism / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011467:Prostate / Q000187:drug effects* / Q000196:embryology / Q000473:pathology*; D011472:Prostatitis / Q000139:chemically induced*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000494:pharmacology
D004965:Estrogen Antagonists; D004968:Estrogens, Non-Steroidal; D007306:Insecticides; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol; D008731:Methoxychlor