Thyroid hormone (T3) has a profound influence on normal development, differentiation and metabolism, processes which are known to be regulated by the transcriptional coactivator PGC-1alpha (peroxisome proliferator-activated receptor gamma coactivator-1alpha). Since T3 rapidly induces PGC-1alpha expression, we investigated whether reduced PGC-1alpha levels lead to alterations in T3-mediated gene expression patterns. Using RNA interference, we reduced PGC-1alpha mRNA to approximately 10% of its initial concentration in rat pituitary GC cells. Knock-down of PGC-1alpha is accompanied by diminished protein concentration and decreased expression level of PGC-1alpha target genes, among them key enzymes involved in gluconeogenesis, mitochondrial biogenesis and fatty acid oxidation. PGC-1alpha, PGC-1beta and NRF-1 mRNA molecules were rapidly degraded with a half-life time of approximately 90min, but this was independent of T3 stimulation. Expression of T3-target genes was not changed upon knock-down of PGC-1alpha. Our data indicate that complex T3-mediated gene expression patterns are maintained independently of PGC-1alpha activation.
