scholarly journals Highly chlorinated PCBs inhibit the human xenobiotic response mediated by the steroid and xenobiotic receptor (SXR).

2004 ◽  
Vol 112 (2) ◽  
pp. 163-169 ◽  
Author(s):  
Michelle M Tabb ◽  
Vladyslav Kholodovych ◽  
Felix Grün ◽  
Changcheng Zhou ◽  
William J Welsh ◽  
...  
Keyword(s):  
Steroid And Xenobiotic Receptor ◽  
Xenobiotic Response ◽  
Xenobiotic Receptor

scholarly journals Acetyl Tributyl Citrate, the Most Widely Used Phthalate Substitute Plasticizer, Induces Cytochrome P450 3A through Steroid and Xenobiotic Receptor

2011 ◽  
Vol 123 (2) ◽  
pp. 460-470 ◽  
Author(s):  
Akira Takeshita ◽  
Junko Igarashi-Migitaka ◽  
Kazusa Nishiyama ◽  
Hideyo Takahashi ◽  
Yasuhiro Takeuchi ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 3A ◽  
Steroid And Xenobiotic Receptor ◽  
Acetyl Tributyl Citrate ◽  
Xenobiotic Receptor

scholarly journals Expression of steroid and xenobiotic receptor in uterine carcinosarcoma, leiomyosarcoma and endometrial stromal sarcoma

2013 ◽  
Vol 5 (3) ◽  
pp. 835-839 ◽  
Author(s):  
XIAONI YUE ◽  
HIROKI UTSUNOMIYA ◽  
JUN-ICHI AKAHIRA ◽  
FUMIHIKO SUZUKI ◽  
KIYOSHI ITO ◽  
...  
Keyword(s):  
Endometrial Stromal Sarcoma ◽  
Uterine Carcinosarcoma ◽  
Stromal Sarcoma ◽  
Steroid And Xenobiotic Receptor ◽  
Xenobiotic Receptor

scholarly journals Mitotane induces CYP3A4 expression via activation of the steroid and xenobiotic receptor

2012 ◽  
Vol 216 (3) ◽  
pp. 297-305 ◽  
Author(s):  
Akira Takeshita ◽  
Junko Igarashi-Migitaka ◽  
Noriyuki Koibuchi ◽  
Yasuhiro Takeuchi
Keyword(s):  
Gene Expression ◽  
Enzyme Activity ◽  
Drug Interactions ◽  
Luciferase Reporter ◽  
Pcr Analysis ◽  
Metabolic Clearance ◽  
Mrna Levels ◽  
Steroid And Xenobiotic Receptor ◽  
Cyp3a4 Enzyme ◽  
Xenobiotic Receptor

Adrenocortical carcinoma (ACC) is a rare disease with an extremely poor prognosis. Mitotane alone or in combination with other cytotoxic drugs is a common therapeutic option for ACC. In addition to its adrenolytic function, mitotane has been known for decades to increase the metabolic clearance of glucocorticoids. It was recently shown that the tyrosine kinase inhibitor sunitinib is also rapidly metabolized in patients treated with mitotane, indicating that mitotane engages in clinically relevant drug interactions. Although the precise mechanism of these interactions is not well understood, cytochrome P450 mono-oxygenase 3A4 (CYP3A4) is a key enzyme to inactivate both glucocorticoids and sunitinib. The nuclear receptor steroid and xenobiotic receptor (SXR (NR1I2)) is one of the key transcriptional regulators ofCYP3A4gene expression in the liver and intestine. A variety of xenobiotics bind to SXR and stimulate transcription of xenobiotic-response elements (XREs) located in theCYP3A4gene promoter. In this study, we evaluated the effects of mitotane on SXR-mediated transcriptionin vitroby luciferase reporter analysis, SXR–steroid receptor coactivator 1 (SRC1) interactions, quantitative real-time PCR analysis ofCYP3A4expression, SXR knockdown, and CYP3A4 enzyme activity assays using human hepatocyte-derived cells. We found that mitotane activated SXR-mediated transcription of the XREs. Mitotane recruited SRC1 to the ligand-binding domain of SXR. Mitotane increasedCYP3A4mRNA levels, which was attenuated by SXR knockdown. Finally, we showed that mitotane increased CYP3A4 enzyme activity. We conclude that mitotane can induceCYP3A4gene expression and suggest that mitotane is used cautiously due to its drug–drug interactions.

scholarly journals Evaluating the Role of the Steroid and Xenobiotic Receptor (SXR/PXR) in PCB-153 Metabolism and Protection against Associated Adverse Effects during Perinatal and Chronic Exposure in Mice

2020 ◽  
Vol 128 (4) ◽  
pp. 047011
Author(s):  
Riann Jenay Egusquiza ◽  
Maria Elena Ambrosio ◽  
Shuyi Gin Wang ◽  
Kaelen Marie Kay ◽  
Chunyun Zhang ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Chronic Exposure ◽  
Steroid And Xenobiotic Receptor ◽  
Xenobiotic Receptor
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