INFLUENCE OF THYROID-HORMONE ON THE TISSUE-SPECIFIC EXPRESSION OF CYTOCHROME-C-OXIDASE ISOFORMS DURING CARDIAC DEVELOPMENT

In mammals, cytochrome c oxidase (COX) is composed of 13 different pro tein subunits. In the rat, two nuclear-encoded subunits, COX VIa and V III, exist as tissue-specific isoforms: heart and liver. Using Norther n-blot analysis, the levels of transcripts for the heart and liver iso forms of VIa and VIII were examined in developing rat hearts. The live r isoform was found to be the predominant form of subunit Via and the exclusive form of MII in the 18-day fetal hearts. The mRNA levels of t he heart isoform of both subunits increased dramatically to reach adul t levels by 14 days. Although the levels of the VIa- and VIII-liver is oform mRNAs remained stable throughout early development, their levels decreased by 40 and 36% respectively between the 18-day fetal stage a nd 18-day neonatal stage. Therefore the upregulation of the heart isof orms and down-regulation of the liver isoforms appear to be regulated in a co-ordinated manner during development. To determine if thyroid h ormone influences the expression of these developmentally regulated is oforms, the RNA was also extracted from the hearts of 2-week-old hypot hyroid rats. The results showed that the levels of VIII-heart and VIa- liver COX mRNAs were approx. 40% lower in the hypothyroid hearts, whil e VIII-liver and VIa-heart COX isoform expression remained unchanged. These data demonstrate that the isoforms of COX subunits VIa and VIII are not co-ordinately regulated by changes in thyroid hormone levels. Therefore we conclude that, although thyroid hormone influences the ex pression of isoforms, it appears to do so via a different mechanism fr om that which regulates the developmental transition.