Figure 1.

Dexamethasone depletes corticosterone levels in blood and glucocorticoid target tissues, while corticosterone add-on partially restores this. Mice received a high-fat diet mixed with dexamethasone (DEX) or vehicle (VEH) and were subcutaneously implanted with low-dose (5 mg) corticosterone (CORT) or vehicle pellets for 3.5 weeks. (A) After DEX, plasma CORT levels were not detected (n.d.) at AM (ZT1) and PM (ZT11) of the light phase at day 8. (B, C) DEX strongly reduced adrenal and spleen weight. (D, E) Using LC-MS analysis, DEX levels were 100-fold higher in liver than in gonadal white adipose tissue (gWAT). (F, G) In gWAT and liver, DEX strongly suppressed CORT levels, which were (partially) restored by DEX + CORT. (H, I) DEX suppressed 11-dehydrocorticosterone levels in gWAT but not in liver. (J, K) 11βHsd1 expression was upregulated by DEX and DEX + CORT in gWAT and downregulated by DEX in liver. Statistical significance was calculated using 2-way ANOVA analysis in (B-K), and 3-way ANOVA analysis in (A) Depicted below the graphs are the P-values of the ANOVA tests for either time (T), CORT (C), DEX (D) or the interaction between CORT and DEX (I). *P < 0.05, ** P < 0.01, ***P < 0.001. 'ns' means 'not significant'. n.d. means 'not detected'.