T3-mediated gene expression is independent of PGC-1α

Abstract 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-1α (peroxisome proliferator-activated receptor γ coactivator-1α). Since T3 rapidly induces PGC-1α expression, we investigated whether reduced PGC-1α levels lead to alterations in T3-mediated gene expression patterns. Using RNA interference, we reduced PGC-1α mRNA to ∼10% of its initial concentration in rat pituitary GC cells. Knock-down of PGC-1α is accompanied by diminished protein concentration and decreased expression level of PGC-1α target genes, among them key enzymes involved in gluconeogenesis, mitochondrial biogenesis and fatty acid oxidation. PGC-1α, PGC-1β and NRF-1 mRNA molecules were rapidly degraded with a half-life time of ∼90 min, but this was independent of T3 stimulation. Expression of T3-target genes was not changed upon knock-down of PGC-1α. Our data indicate that complex T3-mediated gene expression patterns are maintained independently of PGC-1α activation.