Figure 5
From: Dimorphic metabolic and endocrine disorders in mice lacking the constitutive androstane receptor
Sexually dimorphic activity of CAR in the liver: distinct regulation of steroidogenesis genes between males and females. Analysis of hepatic transcriptome of WT and CAR−/− male and female mice at age 16 weeks (n = 6 per group). Heat-map of averaged gene expression values per condition; the hierarchical clustering was obtained from individual expression values using Pearson correlation coefficient as distance and Ward’s criterion for agglomeration. The expression levels are averaged across for the 4 conditions, WT male, CAR−/− male, WT female, CAR−/− female. Red and green indicate values above and below the mean averaged, centered and scaled expression values (Z-score), respectively (A). Black indicates values close to the mean. Venn diagrams representing the number of hepatic genes specifically upregulated (B) or downregulated (C) in CAR−/− mice. Histograms of enrichment score for each pathway. Gene number and corresponding p-value to the right of the histograms. Expression profiles of hepatic genes involved in steroidogenesis pathways in CAR−/− male and females (D). 31 probes were selected as differentially regulated in CAR−/− male and females, respectively (p-value interaction (genotype–sex) < 0.05, n = 6 per group. (E) The DEG lists (FDR = 0,05) of altered mRNAs in the microarray of CAR−/− male and female mouse livers were compared in Correlation Engine (Illumina) to the gene lists of liver signatures for STAT5B (GSE60253), GHR (GSE11396), LXRαβ (GSE38083), AhR (GSE10082), HNF4α (GSE10390) and NRF2 (GSE864) and SREBP1a (GSE53397). Positive correlation was shown by (-log (p-value overlap) > 4).
