Effects of metolachlor on transcription of thyroid system-related genes in juvenile and adult Japanese medaka (Oryzias latipes).

Metolachlor (MT) is one of the most important pesticides applied to corn and other crops for controlling broadleaf and grass weeds. However, the effects of MT on the thyroid system in fish remain to be elucidated. In the present experiment, transcription of genes related to the thyroid system, including thyrotropin releasing hormone (Trh), deiodinase 2 (Dio2), thyroid hormone receptor α (Thrα), and thyroid hormone receptor β (Thrβ), were induced by MT in a sex-, developmental stage-, and tissue- specific manner when medaka were exposed to various concentrations of MT for 14 days. The transcriptional levels of the genes were only significantly altered in both juvenile and adult female medaka in response to MT exposure. And the lowest concentrations able to significantly induce transcription of the selected genes were 10 and 100 μg/L in juvenile and adult female medaka, respectively. In adult female medaka, a significant up-regulation of these genes was detected only in the brain, with little or no effect in the liver. Furthermore, MT-induced (100 μg/L) transcription of thyroid system-related genes was enhanced significantly in male juvenile medaka in the presence of estrogen (E2) (50 and 100 ng/L). Moreover, the mRNA levels of Thrα and Thrβ in males increase with the combined treatments of 100 μg/L MT and 100 ng/L E2. Dio2 increased when exposed to 100 μg/L MT and 50 or 100 ng/L E2. The information obtained in the present study suggests that MT has the potential to influence several steps of the hypothalamus-pituitary-thyroid (HPT) axis homeostasis and to disrupt the thyroid system in medaka.