Abstract
Methoxychlor (MXC) is primarily used as a pesticide and widely present in the environment. The objective of the present study is to investigate the direct effects of MXC and its metabolite 2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE) on two isoforms of 11β-hydroxysteroid dehydrogenase (11β-HSD1 and 11β-HSD2) in vitro. Human liver microsome, rat testis microsome and adult Leydig cells were used for the measurement of 11β-HSD1 activity. Human placental and rat kidney microsomes were used for 11β-HSD2 activity. The IC50 values on human 11β-HSD1 by MXC and HPTE were 1.91±0.07 and 8.88±0.08μM, respectively. HPTE inhibited rat 11β-HSD1 with IC50 of 9.15±0.05μM, while MXC did not inhibit the enzyme. MXC and HPTE were competitive inhibitors of 11β-HSD1. HPTE also inhibited human and rat 11β-HSD2 with IC50 values of 55.57±0.08 and 12.96±0.11μM, respectively, while MXC did not inhibit 11β-HSD2. In summary, our results showed that MXC and its metabolite HPTE inhibited both isoforms of 11β-HSD in a species- and chemical structure-dependent manner.
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