In utero exposure to antiandrogens alters the responsiveness of the prostate to p,p'-DDE in adult rats and may induce prostatic inflammation.
DDE is an environmental pollutant with antiandrogenic properties. Following administration to pregnant rats, DDE was shown to cause feminization in the male offspring at the neonatal stages but did not affect the pubertal growth of accessory sex organs. In this study, we examined the potential of in utero exposure to antiandrogens to alter the responsiveness of the male rats to subsequent DDE challenge. Pregnant Long-Evans rats were dosed by gavage from Gestation Day 14 to 18 at 0, 10 (low dose), or 100 (high dose) mg DDE, or 40 mg flutamide/kg body wt (bw)/day (in utero treatment). At approximately 80 days of age, the male offspring from each of the four in utero treatment groups were divided into two groups. One group received the adult treatment of four daily gavage administrations of DDE at 70 mg/kg bw (adult treatment), while the second group served as the adult treatment control (adult control). The in utero treatment resulted in 18, 31, and 53% reductions of ventral prostate weights at approximately 85 days of age compared to the control for the low- and high-dose DDE and flutamide groups, respectively. These results suggest that the in utero antiandrogen treatments produced a latent effect on prostate growth that became pronounced only in the postpubertal stage. The in utero treatment also altered the responsiveness of the prostate to the adult treatment, indicated by a significant reduction in ventral prostate weight that was seen only in the control group of the in utero treatment but not in the other groups. The in utero treatment was also associated with expression of testosterone-repressed prostatic message-2 in the adult ventral prostate. In addition, a few prostates in the high-dose DDE- and flutamide-treated groups of the in utero treatment were found to have chronic suppurative prostatitis. While other types of hormonal manipulations have been shown to incite similar responses in rat prostate, the possible linkage between in utero antiandrogen treatment and prostatic inflammation needs to be further evaluated.
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Chemical Industry Institute of Toxicology, 6 Davis Drive, North Carolina, 27709-2137, USA. you@ciit.org
Brenneman
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D000273:Adipose Tissue / Q000378:metabolism; D000284:Administration, Oral; D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D015152:Blotting, Northern; D051152:Clusterin; D003633:Dichlorodiphenyl Dichloroethylene / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D005485:Flutamide / Q000633:toxicity*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics; D008099:Liver / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D018832:Molecular Chaperones; D009929:Organ Size / Q000187:drug effects; D010446:Peptide Fragments / Q000235:genetics; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011467:Prostate / Q000187:drug effects* / Q000473:pathology; D011472:Prostatitis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D013739:Testosterone / Q000097:blood
D000726:Androgen Antagonists; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones; D010446:Peptide Fragments; D012333:RNA, Messenger; C068142:glyceraldehyde 3-phosphate dehydrogenase (304-313); D013739:Testosterone; D003633:Dichlorodiphenyl Dichloroethylene; D005485:Flutamide; D007986:Luteinizing Hormone; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases