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. 2017 Sep 18;12(9):e0184842. doi: 10.1371/journal.pone.0184842

Fig 6. AhR-mediated changes in sexually dimorphic regulator expression.

Fig 6

(A) GHR-JAK2-STAT5 signaling cascade interactions with liver-specific gene expression regulators [16, 18, 19, 43]. GH-mediated activation of GHR induces STAT5 phosphorylation promoting male-specific gene expression, and induction of female-specific CUX2 (red outline) which regulates female-specific gene expression. CUX2 and STAT5 compete for binding sites resulting in sexually dimorphic gene expression. BCL6, HNF4α, HNF6, and FOXA also regulate sexually dimorphic and liver-specific gene regulation. Blue identifies repressed genes while white represents genes unaffected by TCDD. (B) Heatmap of sexually dimorphic and liver-specific gene expression regulators (A) in males (28d) and females (28 and 92d). Genes in blue were repressed while red indicates induction. STAT5 protein levels were determined in (C) female and (D) male mice gavaged with 30 μg/kg TCDD every 4 days for 28 days. Bars represent mean ± SEM for at least 3 animals (N = 3–4). Asterisks (*) indicate a significant difference compared to vehicle control as determined by Mann-Whitney U-test.