ABSTRACT
Background Arsenic can enter the hypothalamus to induce estrogen effect and interfere with the function of the neuroendocrine system. The thyroid endocrine system (hypothalamic-pituitary-thyroid axis) is one of the main endocrine systems, and the mechanism of arsenic-induced thyroid endocrine toxicity is still unclear. Objective To investigate the effects of different arsenic exposure levels on estradiol (E2), hypothalamic thyrotropin-releasing hormone (TRH), and their receptor (ERα, ERβ, and TRHR) mRNAs in rats and the possible hypothalamic toxic pathway and mechanism. Methods Seventy Wister rats were randomly divided a control group (sterile water); low-, medium-, and high-dose arsenic exposure groups [0.8, 4.0, and 20.0 mg·kg−1 sodium arsenite (NaAsO2)]; estrogen receptor inhibitor (ICI182780) intervention + low-, medium-, and high-dose arsenic exposure groups; with 10 animals in each group, half male and half female. Rats in the arsenic exposure groups were exposed to NaAsO2 by drinking water for 19 weeks, and rats in the intervention groups were injected with 0.5 mg·kg−1 ICI182780 via tail vein at week 9, 3 times a week. The levels of E2 and TRH in serum of rats were detected by ELISA. The expression levels of estrogen receptor α (ERα), estrogen receptor β (ERβ), and TRH receptor (TRHR) mRNAs in hypothalamus of rats were detected by real-time PCR (RT-PCR). Results (1) E2 and its receptor mRNA: Compared with the control group, the serum E2 level of female rats was increased in the low-dose and the medium-dose arsenic exposure groups (P<0.05), and the serum E2 level of male rats was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), and the change of female E2 was greater than that of male rats. Compared with the control group, the relative expression levels of ERα mRNA and ERβ mRNA in female rats were increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), so were the relative expression levels of ERα mRNA in male rats (P<0.05). (2) TRH and its receptor mRNA: Compared with the control group, the serum TRH level of female rats was increased in the high-dose arsenic group (P<0.05), the relative expression level of TRHR mRNA was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05). Results (1) and results (2) suggested that females were more likely than males to have abnormal changes in E2, TRH, and related receptor genes after arsenic exposure. (3) Compared with female rats in the medium-high dose arsenic exposure group, the expressions of TRH and TRHR induced by arsenic exposure were inhibited after the intervention of ICI182780 (P<0.05), suggesting that arsenic in the hypothalamus may have toxic effects on TRH and TRHR by inducing estrogen-like effects. Conclusion Arsenic exposure can induce estrogen-like effects in the hypothalamus, interfere with thyroid function, and show dose-dependent and sex differences. E2 and TRH and their receptors may be the toxic pathway of arsenic-related estrogen-like effect.
ABSTRACT
ObjectiveTo investigate the expression of thyrotropin-releasing hormone receptor (TRH-R) type-1and type-2 in ethane dimethanesulphonate (EDS)-treated rat testis, and to discuss the significance of its expression in Leydig cells.Methods To make the injured testis Leydig cells rat model with EDS treatment. Western blotting, immunohistochemical ABC and immunofluorescence double labeling methods were used to detect the expression and location of TRH-R1 and R2 in the testicular tissues of EDS-treated-day 2,day 7,day 14,day 21 and day 28 rat mode, respectively. Results Western blotting results showed that the positive immunochemical staining was not found in the testicular tissues of the EDS-treated day 2 to day 14, on the other hand,they were found in EDS-treated-21 day and EDS-treated-28 day. Immunohistochemistry demonstrated that TRH-R1 and R2 expressed in the spindle-shaped cells reappeared around seminiferous tubules of post-EDS 21 days and 28 days groups. Immunofluorescence double labeling confirmed that these TRH-R1 and R2 positively stained cells were newly regenerated progenitor Leydig cells.Conclusion TRH-R1 and R2 are involved in the regeneration of Leydig cells in EDS-treated rat testis, and they may exert functions in the proliferation and differentiation of adult type Leydig cells.