The effects of MCP on the thyroid endocrine system in females, however, remain unclear. THs are synthesized and secreted by the thyroid follicles under the control of the HPT axis. In teleosts, the thyrotropin-releasing hormone and/or corticotrophin-releasing hormone, released from the hypothalamus, coordinate the HPT axis function by controlling the release of thyrotropin from the pituitary, which could stimulate TH synthesis and release. Most of the plasma THs in fish are bound to transthyretin and only free hormones can enter target cells to elicit a response. In the liver and some other peripheral tissues, three types of deiodinases are known to control the conversion of T4 to the more physiologically active T3 or the production of metabolically inactive counterparts. Such complex regulatory pathways are involved in thyroid homeostasis. Therefore, environmental chemicals can act at multiple stages in the HPT axis. An increasing number of studies have reported that groups of pesticides, Erlotinib including acetochlor, amitrole, and metolachlor, have the potential to influence several steps in HPT axis homeostasis and to induce THs disturbance in adult fish, particularly with respect to sex differences occurring in response to chemicalinduced thyroid system disruption. For example, Li et al. showed that TH-related genes such as malic enzyme and sodium iodide symporter were significantly down-regulated in the brains of the rare minnow Gobiocypris rarus, and that the expression of these genes in females was more sensitive to acetochlor than that in males. Recently, we found that a 21-d exposure to MCP pesticide caused significant decreases in plasma TT3 levels and TT3-to-TT4 ratios in male goldfish ; however, whether similar effects occur in females is not clear. In the present study, although the plasma levels of TT4 remained unchanged, those of TT3, FT4, and FT3 in female goldfish were significantly altered after a 21-day exposure to MCP pesticide, suggesting a failed adaptation and auto-regulation of THs homeostasis. Almost all THs circulating in the plasma are bound to transporter proteins, and the equilibrium of TH binding to the plasma proteins determines the concentration of free THs within the plasma. TTR, which is primarily a secretory product of the liver, has been proposed to be the major TH-carrier protein that binds THs and transports them to target tissues in fish. In our study, TTR gene expression was up-regulated after exposure to 0.01 and 0.10 mg/L MCP pesticide. This upregulation might have resulted in higher TTR mRNAs and thus TTR proteins, leading to decreases in plasma FT3 and/or FT4 levels. Moreover, the expression of ttr showed a positive correlation with plasma FT4 levels in females. Notably, less than 1% of plasma TT4 is free with 99% reversibly bound to plasma proteins. Indeed, changes of such small amount of FT4 contents may not represent a dynamic circulating TT4 reservoir and vice verse. For example, in brown trout fed diets enriched with b–Tetrabromoethylcyclohexane for 56 days, there was no significant difference among treatments in FT4, but TT4 was significantly reduced in the high dose group relative to the control. In the 0.01 mg/L MCP group in particular, one possible explanation for the increased plasma FT4 levels could be that feedback systems attempt to respond to the reduction in plasma TT3 levels. However, the stimulatory effects of 0.01 mg/L MCP pesticide on plasma FT4 levels in females were not observed in males, indicating that the thyroidal system in female goldfish is more sensitive to MCP than that of males.