Figure 4(A, B) The effect of hypoxia on the GR response to DEX stimulation was studied via RNA-seq, n=3 per group. Venn diagram depicting the number of genes upregulated (up) or downregulated (dn) by DEX in normoxia and by hypoxia after 6h (A) or 24h (B) (LFC > 1 or LFC < -1 and P ≤ 0.05). (C) Heatmap representing log2 values of shared stress GRE genes (counts) induced by hypoxia 6h and 24h and induced by DEX in normoxia (LFC > 1 and P ≤ 0.05). (D-G) Female C57BL/6J and ADX mice were put in normoxia or hypoxia for 6h or 24h, n=6/group, two independent experiments. (D, E) Confirmation of RNA-seq data via RT-qPCR [6h (D) or 24h (E)]. (F, G) Plasma GC concentration [6h (F) or 24h (G)]. Data information: All bars represent mean ± SEM. P-values were calculated using two-way ANOVA followed by post-hoc Šídák's multiple comparisons test to correct for multiple testing during the pairwise multiple comparisons, except if otherwise stated. ****P<0.0001, ***P<0.001, **P<0.01, *P≤0.05. (H-J) Female C57BL/6J mice were put in normoxia or hypoxia for the indicated time points (2h, 6h and 24h). (H) Hypothalamic Crh mRNA expression levels were determined via RT-qPCR. (I) ACTH levels were measured in the plasma. N=3-5 per group, one experiment. P-values were analysed with one-way ANOVA. (J) Plasma GC concentration, mice in normoxia are depicted as black circles, mice in hypoxia are depicted as white squares. N=5-6 per group. Data information: All bars represent mean ± SEM. P-values were calculated using two-way ANOVA followed by post-hoc Šídák's multiple comparisons test to correct for multiple testing during the pairwise multiple comparisons, except if otherwise stated. ****P<0.0001, ***P<0.001, **P<0.01, *P≤0.05. (K) Female C57BL/6J mice were put in normoxia or hypoxia for 6h and injected i.p. with 5 mg RU486 or vehicle (DMSO). Liver was isolated and stress GRE gene expression was measured via RT-qPCR. N=5 per group, one experiment. Data information: All bars represent mean ± SEM. P-values were calculated using two-way ANOVA followed by post-hoc Šídák's multiple comparisons test to correct for multiple testing during the pairwise multiple comparisons, except if otherwise stated. ****P<0.0001, ***P<0.001, **P<0.01, *P≤0.05. (L) Female WT and GRdim/dim mice were put in normoxia or hypoxia for 6h and liver was isolated. Stress GRE gene expression was measured via RT-qPCR. N=5-9 per group, two independent experiments. Data information: All bars represent mean ± SEM. P-values were calculated using two-way ANOVA followed by post-hoc Šídák's multiple comparisons test to correct for multiple testing during the pairwise multiple comparisons, except if otherwise stated. ****P<0.0001, ***P<0.001, **P<0.01, *P≤0.05. (M) HIF1aHIF2afl/fl and HIF1aHIF2aAlbKO mice were put in hypoxia for 6h. Stress GRE genes were measured in the liver via RT-qPCR. N=4 per group, one experiment. Data information: All bars represent mean ± SEM. P-values were calculated using two-way ANOVA followed by post-hoc Šídák's multiple comparisons test to correct for multiple testing during the pairwise multiple comparisons, except if otherwise stated. ****P<0.0001, ***P<0.001, **P<0.01, *P≤0.05. (N) Expression levels of DEX responsive genes in normoxia and unique DEX responsive genes induced by hypoxia were measured in the liver of ADX mice after DEX stimulation during hypoxia (24h) via RT-qPCR. N=3-4 per group, one experiment. Data information: All bars represent mean ± SEM. P-values were calculated using two-way ANOVA followed by post-hoc Šídák's multiple comparisons test to correct for multiple testing during the pairwise multiple comparisons, except if otherwise stated. ****P<0.0001, ***P<0.001, **P<0.01, *P≤0.05.