Coordinate induction of multiple cytochrome c mRNAs in response to thyroid hormone

Because of the well documented influence of thyroid hormones in the general control of oxidative metabolism and their putative role in the transcriptional activation of specific genes, changes in the levels of multiple cytochrome c mRNAs were monitored in thyroidectomized rats after administration of 3,5,3'-triiodo-L-thyronine. In contrast to normal animals where the concentration of cytochrome c mRNAs in the polyadenylated RNA fraction is approximately 4- to 5-fold higher in kidney than in liver, hypothyroid animals displayed an equivalent low level of all three mRNAs (1400, 1100, and 700 nucleotides) in both tissues. Following the establishment of chronic hyperthyroidism, the levels of the three mRNAs were coordinately elevated by about 4- to 5-fold resulting in their restoration to approximately normal amounts for kidney but to a level substantially above the normal for liver. Only modest induction of mRNA is detected in the first 12 h following a single intravenous injection of 3,5,3'-triiodo-L-thyronine. The major increase occurs between 12 and 24 h with the plateau level attained between 24 and 48 h. The magnitude of the response is in excess of the general increase in total cellular RNA mediated by the hormone. Induction of the cytochrome c mRNAs is coincident with an elevation in gene transcription of comparable magnitude detected using nascent RNA chains synthesized by isolated nuclei. The kinetics of these responses are similar to those observed for the increase in respiratory activity mediated by the hormone.