ArticleLaboratory investigation; a journal of technical methods and pathology2018
Establishment and analysis of a mouse model that regulates sex-related differences in liver drug metabolism.
Article in Laboratory investigation; a journal of technical methods and pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 34 citations in OpenAlex.
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- Hypothalamic BCL6 signaling modulates energy homeostasis and metabolism by inhibiting STAT3 transcription.Journal of advanced research · 2026Article
- KDM5C and KDM5D influence DNA methylation in adult mouse liver.Biology of sex differences · 2026Article
- Survey of gene, lncRNA and transposon transcription patterns in four mouse organs highlights shared and organ-specific sex-biased regulation.Genome biology · 2025Article
- Review
- Carboxylesterase 1d Inactivation Augments Lung Inflammation in Mice.ACS pharmacology & translational science · 2022Article
- Interplay Between GH-regulated, Sex-biased Liver Transcriptome and Hepatic Zonation Revealed by Single-Nucleus RNA Sequencing.Endocrinology · 2022Article
- B-cell lymphoma 6 alleviates nonalcoholic fatty liver disease in mice through suppression of fatty acid transporter CD36.Cell death & disease · 2022Article
- Harnessing natural variation to identify cis regulators of sex-biased gene expression in a multi-strain mouse liver model.PLoS genetics · 2021Article
- Early expression of requisite developmental growth hormone imprinted cytochromes P450 and dependent transcription factors.Endocrine connections · 2021Article
- Distinct roles of androgen receptor, estrogen receptor alpha, and BCL6 in the establishment of sex-biased DNA methylation in mouse liver.Scientific reports · 2021Article
- INPP4B protects from metabolic syndrome and associated disorders.Communications biology · 2021Article
- Article
- Dynamic repression by BCL6 controls the genome-wide liver response to fasting and steatosis.eLife · 2019Article
- Sex-Related Differences in Immune Response and Symptomatic Manifestations to Infection withJournal of immunology research · 2019Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The adult liver performs many metabolic functions for maintaining homeostasis. There are several sex differences in liver function and disease pathogenesis. One important function of the liver is drug metabolism, where cytochrome p450s (CYPs) in hepatocytes are the main enzymes involved. The toxicity of various drugs and chemicals differs with sex due to differences in hepatocytic CYP expression. However, the molecular mechanism regulating sex-related differences in drug metabolism remains unknown. In this study, we identified transcriptional regulator B-cell lymphoma 6 (Bcl6) as an important factor in sex-biased differential CYP expression. Microarray analysis of livers derived from liver-specific Bcl6-knockout mice showed that Bcl6 is required for sex-biased CYP expression patterns in the liver. Additionally, quantitative PCR analysis revealed that hepatocytic expression of male-biased genes, such as Cyp2d9, Cyp2u1, Cyp4a12a/12b, and Cyp7b1, in liver-specific Bcl6-knockout male mice significantly decreased to levels similar to those observed in wild-type female mice. Conversely, hepatocytic expression of female-biased genes, such as Cyp2a4/2a5, Cyp2b9, Cyp3a41, and Cyp17a1, significantly increased in liver-specific Bcl6-knockout male mice. Deletion of Bcl6 caused female-like expression of CYPs in male livers. These results suggest that Bcl6 is a key regulator of sex-related differential regulation of drug metabolism. Moreover, serum sex hormone levels and fertility did not change in liver-specific, Bcl6-knockout mice. Hepatocytic Bcl6 regulates sex-related differential CYP expression in the liver without changing the sex of the whole body. Thus, this mouse model is useful for analyzing liver-specific sex-dependent regulation of drug metabolism and pathogenesis.
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