Prepubertal exposure to compounds that increase prolactin secretion in the male rat: effects on the adult prostate.
To test the hypothesis that a transient increase in prolactin (PRL) secretion prior to puberty can result in an alteration of the adult prostate, male rats were exposed from postnatal Days (PND) 22 to 32 to compounds that increase PRL secretion. These compounds included pimozide (a dopamine antagonist), estradiol-17beta, and bisphenol A (a monomer of polycarbonate plastics reported to have weak estrogenic activity). During dosing, pimozide (PIM), bisphenol A (BPA), and estradiol-17beta (E(2)) stimulated an increased secretion of PRL. At 120 days of age, the lateral prostate weight was increased in the PIM and BPA groups as compared to the vehicle-injected controls. Examination of the prostates revealed inflammation in the lateral lobes of all treated groups. Results of a myeloperoxidase assay, a quantitative assay to assess acute inflammation, indicated an increase in the percentage of males with neutrophil infiltrate in the lateral prostates of the PIM and E(2) treatment groups compared to their respective controls. The histological evaluations of these tissues confirmed an increase in luminal polymorphonuclear cells and interstitial mononuclear cells of the lateral prostates in all treatment groups. Administration of the dopamine agonist, bromocriptine, to the estradiol-implanted males from PND 22 to 32 reversed the induction of lateral prostate inflammation by estradiol, suggesting that PRL was necessary for the inflammatory effect. This study demonstrates that prepubertal exposures to compounds that increase PRL secretion, albeit through different mechanisms, can increase the incidence of lateral prostate inflammation in the adult.
Stoker
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Endocrinology Branch, Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. tammy@epa.gov
Robinette
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Britt
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Laws
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Cooper
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D000375:Aging; D000818:Animals; D001559:Benzhydryl Compounds; D018492:Dopamine Antagonists / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D005260:Female; D008297:Male; D009929:Organ Size; D009195:Peroxidase / Q000032:analysis; D010636:Phenols / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D011467:Prostate / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000209:etiology; D011472:Prostatitis / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012741:Sexual Maturation; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D018492:Dopamine Antagonists; D004958:Estradiol; D004968:Estrogens, Non-Steroidal; D009195:Peroxidase; D010636:Phenols; D010868:Pimozide; D011388:Prolactin; C006780:bisphenol A; D000098826:Bisphenol A Compounds