| Summary: | 碩士 === 國立臺灣大學 === 生命科學系 === 104 === Activation of aryl hydrocarbon receptor (AHR) by xenobiotic toxic chemicals such as 2,3,7,8-tetrachlorodibenzo-p-dioxin regulates a variety of cellular processes, for example, embryogenesis, tumorigenesis and inflammation. However, the identity of endogenous ligands activating AHR remains unclear. To explore the possibilities, previously developed cell free bioassay for dioxin-like compounds in our laboratory was applied and Tetrahydrocorticosterone (THB) was identified from zebrafish embryos as a potential AHR ligand. In this study, we aim to investigate the functions of THB in AHR activation and further physiological effects. In vitro studies revealed that THB induces AHR translocation into nucleus and activates the expression of downstream cytochrome P450 1A1 (CYP1A1). THB also demonstrated potential to promote neuronal differentiation in neuroblastoma (NB) cells, which corresponds to our previous studies that AHR overexpression lead to NB cells differentiation. On the other hand, In vivo studies indicated that THB treatment enhances AHR-target zCYP1A, myelin-associated myelin basic protein (zMBP) and oligodendrocyte transcription factor 2 (zOLIG2) expression via AHR2-dependent pathway in zebrafish. Moreover, we found that THB is involved in early neurogenesis and neuronal differentiation of oligodendrocyte, astrocyte and microglia via AHR2 pathway. Therefore, our results strongly suggest that THB is an endogenous AHR ligand, and plays a critical role during neuronal differentiation.
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