Estrogenic effects in vitro and in vivo of the fungicide fenarimol.
The fungicide fenarimol has the potential to induce endocrine disrupting effects via several mechanisms since it possesses both estrogenic and antiandrogenic activity and inhibits aromatase activity in cell culture studies. Hence, the integrated response of fenarimol in vivo is not easy to predict. In this study, we demonstrate that fenarimol is also estrogenic in vivo, causing significantly increased uterine weight in ovariectomized female rats. In addition, mRNA levels of the estrogen responsive gene lactoferrin (LF) were decreased in uteri, serum FSH levels were increased, and T3 levels decreased in fenarimol-treated animals. To our knowledge, only two other pesticides (o,p-DDT and methoxychlor) have previously been reported to induce an estrogenic response in the rodent uterotrophic bioassay. A pronounced xenoestrogenicity in serum samples from rats treated with fenarimol and estradiol benzoate (E2B) separately or in combination was observed, demonstrating the usefulness of this approach for estimating the integrated internal exposure to xenoestrogens. The MCF-7 cell proliferation assay was used to investigate further the dose-response curves for the estrogenic, antiestrogenic, and aromatase inhibiting properties of fenarimol in vitro. The results indicates that fenarimol exhibits a dual effect being aromatase inhibitor at low concentrations and estrogenic at higher concentrations.
Andersen
Helle Raun
HR
Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, Winsløwparken 17, Dk-5000 Odense C, Denmark. hrandersen@health.sdu.dk
Bonefeld-Jørgensen
Eva C
EC
Nielsen
Flemming
F
Jarfeldt
Kirsten
K
Jayatissa
Magdalena Niepsuj
MN
Vinggaard
Anne Marie
AM
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005260:Female; D005659:Fungicides, Industrial / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D007781:Lactoferrin / Q000235:genetics / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D011743:Pyrimidines / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D004968:Estrogens, Non-Steroidal; D005659:Fungicides, Industrial; D011743:Pyrimidines; D012333:RNA, Messenger; D013739:Testosterone; D004958:Estradiol; D007781:Lactoferrin; C033789:fenarimol