Effect of the herbicide pendimethalin on rat uterine weight and gene expression and in silico receptor binding analysis


Undeger U. , Schlumpf M., Lichtensteiger W.

FOOD AND CHEMICAL TOXICOLOGY, cilt.48, ss.502-508, 2010 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 48 Konu: 2
  • Basım Tarihi: 2010
  • Doi Numarası: 10.1016/j.fct.2009.11.001
  • Dergi Adı: FOOD AND CHEMICAL TOXICOLOGY
  • Sayfa Sayıları: ss.502-508

Özet

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. (C) 2009 Elsevier Ltd. All rights reserved.