Tyrosine hydroxylase assay: a bioassay for aryl hydrocarbon receptor-active compounds based on tyrosine hydroxylase promoter activation

Abstract

Tyrosine hydroxylase (TH) assay is a novel bioassay for screening aryl hydrocarbon receptor (AhR)-active compounds with diverse toxicities. The TH assay employs reporter genes to evaluate TH promoter activity, which is linked to dopamine synthesis and regulated by the AhR-aryl hydrocarbon receptor responsive element-III (AHRE-III)-mediated pathway. The toxic equivalency factors for higher chlorinated dioxin congeners in the TH assay (TH-TEF) exhibit the same tendency as those for the WHO-TEF, indicating that the activity of the TH assay is consistent with that of existing methods. Furthermore, other chemicals, such as lower chlorinated dioxin congeners that were minimally investigated in the past could be detected preferentially by this assay.

Tyroxine Hydroxylase-Positive Neuronal Cell Population is Increased by Temporal Dioxin Exposure at Early Stage of Differentiation from Human Embryonic Stem Cells

“…Our study showed an inducible effect of TCDD on the differentiation of TH-positive neuronal cells. The effects of TCDD-AHR signaling on the TH gene and TH-positive cell development were seen in the literature [48,49,50]. The overexpression of Ahr cDNA in the murine neuroblastoma Neuro2a cell induced Th expression [48].…”

“…The overexpression of Ahr cDNA in the murine neuroblastoma Neuro2a cell induced Th expression [48]. A regulatory sequence called Ahr responsive element III (AHRE-III) was identified within the Th gene from the -285 to -167 upstream region [49]. The upregulation of Th gene expression by AHRE-III was evidenced by Neuro2a cell-based reporter assay and TCDD exposure.…”

Ahr and Cyp1a2 genotypes both affect susceptibility to motor deficits following gestational and lactational exposure to polychlorinated biphenyls

“…Bemis and Seegal (2004) reported that PCB mixtures inhibit the vesicular monoamine transporter (VMAT) in synaptosomes from adult Long-Evans rats. Interestingly, Akahoshi et al (2009, 2012) demonstrated that the liganded AHR upregulates tyrosine hydroxylase, the rate-limiting enzyme in dopamine production. Together, this suggests future work is needed to examine the inter-related effects of PCB mixtures on dopamine production, metabolism and transport.…”