title: Effect of the herbicide pendimethalin on rat uterine weight and gene expression and in silico receptor binding analysis.
abstract: The endocrine disrupting potential of the herbicide pendimethalin was investigated in vivo on the uterotrophic response and on the expression of estrogen-regulated genes examined by quantitative real-time RT PCR. Receptor binding characteristics of pendimethalin were analyzed by an in silico method. Pendimethalin (150, 225, 300 and 600 mg/kg/day) was administered by oral gavage to immature female rats for 3 days, with ethinylestradiol (0.001 mg/kg/day) as positive control. Pendimethalin caused a small but significant increase in absolute uterine weight at and above 300 mg/kg/day and in relative uterine weight at 600 mg/kg/day. Estrogen receptor (ER)-alpha mRNA levels were not affected, whereas ER-beta mRNA was up-regulated at the highest dose. Progesterone receptor mRNA level was not significantly changed, while insulin-like growth factor-I mRNA was reduced, significantly at 225 mg/kg/day to 65% of control. Androgen receptor (AR) mRNA showed a marked down-regulation at doses of 225 mg/kg/day and above. The expression pattern differed from that of ethinylestradiol. In silico analysis revealed potential binding of pendimethalin to ER-beta and AR, but virtually no binding to ER-alpha. These data demonstrate that pendimethalin exhibits estrogenic activity also in vivo. However, its uterotrophic effect, which is an ER-alpha-mediated response, is very small, and it appears that in vivo actions should rather be sought in ER-beta-regulated functions.
authors.affiliation: Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Hacettepe University, Sihhiye, Ankara, Turkey. uundeger@hacettepe.edu.tr
authors.forename: U
authors.initials: U
authors.lastname: Undeğer
authors.forename: M
authors.initials: M
authors.lastname: Schlumpf
authors.forename: W
authors.initials: W
authors.lastname: Lichtensteiger
mesh_terms: D000814:Aniline Compounds / Q000633:toxicity*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D019295:Computational Biology; D052244:Endocrine Disruptors / Q000633:toxicity*; D047629:Estrogen Receptor beta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006540:Herbicides / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D011987:Receptors, Steroid / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000814:Aniline Compounds; D052244:Endocrine Disruptors; D047629:Estrogen Receptor beta; D006540:Herbicides; D012333:RNA, Messenger; D011987:Receptors, Steroid; C030856:pendimethalin