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Xenobiotic Biotransformation
Published in Robert G. Meeks, Steadman D. Harrison, Richard J. Bull, Hepatotoxicology, 2020
Transcription of genes encoding P450 for biosynthesis of steroids (androgens, estrogens, glucocorticoids, and mineral corticoids) is responsive to ACTH or FSH, depending on cell type. cAMP is the intracellular messenger mediating the increased transcription. To increase transcription of the P450, cAMP itself acts indirectly by increasing the transcription of a hypothetical steroid hydroxylase-inducing protein. This protein presumably increases transcription by binding to a specific cis-acting genomic control element for the appropriate P450 gene.
2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Environmental Antiestrogens:Characterization and Mechanism of Action
Published in Rajesh K. Naz, Endocrine Disruptors, 2004
Several studies have reported that TCDD and related compounds inhibit diverse hormone/growth factor-mediated responses in animal and cellular models.20 For example, TCDD inhibits epidermal growth factor (EGF) receptor binding or autophosphorylation in multiple species/tissues; however, the role of this response in AhR-mediated toxicity has not been determined.89–94 Treatment of human keratinocytes35 or MDA-MB-46885 human breast cancer cells with TCDD increases TGFα mRNA and protein levels, and this is also accompanied by inhibition of MDA-MB-468 cell growth.85 Subsequent studies showed that the growth-inhibitory response by TCDD was directly related to induction of TGFα, which exhibits antimitogenic activity in this cell line. In contrast, TCDD inhibits the mitogenic activity of TGFα, EGF, and insulin-like growth factor-1 (IGF-1) in MCF-7 or T47D cells.95–97 TCDD modulates several steps in metabolism of cholesterol to various steroid hormones,98,99 and induction of CYP1A1, CYP1A2, and CYP1B1 is associated with increased 2- and 4-steroid hydroxylase activities.100–103 The antiestrogenic activity of AhR agonists has been intensively investigated in several laboratories, and this chapter primarily focuses on this response, which involves complex interactions between the AhR and ER signaling pathways.
Synthesis, Enzyme Localization, and Regulation of Neurosteroids
Published in Sheryl S. Smith, Neurosteroid Effects in the Central Nervous System, 2003
steroid hydroxylase, J. Biol. Chem., 242, 485-491, 1967. Coghlan, V.M. and Vickery, L.E., Expression of human ferredoxin and assembly of
Functional characterization of 21 CYP3A4 variants on amiodarone metabolism in vitro
Published in Xenobiotica, 2019
Cheng-Cheng Yang, Xiang Zheng, Teng-Hui Liu, Chen-Chen Wang, Peng-Fei Tang, Zhe Chen, Bo-Wen Zhang, Ping Fang, Guo-Xin Hu, Jian-Ping Cai
Eiselt et al. (2001) revealed CYP3A4*9, CYP3A4*10 except CYP3A4*11 with a lower turnover of testosterone, were not obviously different when compared with the wild-type in expression or steroid hydroxylase activity. Our results showed all of them importantly increased the Clint values except CYP3A4*9 with no changes compared with the wild type, especially CYP3A4*11 with an extremely increasing clearance rate (435.96%) for AM owing to the increasement of Vmax (5.8-fold, p < 0.05).