Figure 1.
Effect of T3 on gene expression in primary mouse cerebrocortical cell cultures in the presence or absence of TRα1 or TRβ.
Cells (n = 6) from wild type (Wt), TRα1 KO (αKO), or TRβ KO (βKO) mice were incubated for 24 hours in the absence (open bars) or in the presence of 1 nM T3 (filled bars). Statistical analysis was by two-way ANOVA; ns = P>0.05; * = P<0.05; ** = P<0.01; *** = P<0.001.
Figure 2.
Effect of T3 in the presence or absence of cycloheximide (CHX) on gene expression in primary mouse cerebrocortical cell cultures from wild type mice.
The cells (n = 4) were incubated for 30 min with or without CHX (8 µg/ml) before adding T3 (10 nM), and then incubated for 6 hours. Statistical analysis was by one-way ANOVA; ns = P>0.05; * = P<0.05; ** = P<0.01; *** = P<0.001.
Figure 3.
Effects of T3 and all-trans retinoic acid (RA) on gene expression in primary mouse cerebrocortical cell cultures from wild type mice.
The cells (n = 4) were incubated for 48 hours in the absence or presence of T3 (1 nM), RA (1 µM) or both. Statistical analysis was by one-way ANOVA; ns = P>0.05; *** = P<0.001.
Figure 4.
Effects of T3 and dexamethasone (DEX) on gene expression in primary mouse cerebrocortical cell cultures from wild type mice or from TRα1 KO mice.
The cells (n = 4) were incubated for 48 hours in the absence or presence of T3 (1 nM), DEX (10 nM) or both. Statistical analysis was by one-way ANOVA; ns = P>0.05; * = P<0.05; ** = P<0.01; *** = P<0.001.
Figure 5.
A summary of the interactions between T3 receptor subtype, and retinoic acid and glucocorticoid signaling in the T3-mediated control of gene expression described in this work.
T3 induces up regulation (+) or down regulation (−) of gene expression. Specificity of TR subtypes is depicted by a color gradient. Dio3 and Aldh1a1 require TRα1, but no clear preferences were detected for other genes. Transcriptionally direct T3 responses include Shh, Hr, and Klf9. Induction of Shh is probably involved in Dio3 regulation by T3. T3 regulates the expression of enzymes involved in the synthesis and degradation of retinoic acid (RA). The effect of T3 on Klf9 and on Aldh1a1 is potentiated by glucocorticoids, in part by up regulation of the glucocorticoid receptor Nr3c1.