Partial reversal of .alpha.2U globulin gene expression by thyroxine in the liver of diabetic rats

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Abstract
Synthesis of .alpha.2u globulin and its mRNA has been used as an index to monitor the effect of thyroxine on specific gene expression in the liver of hypoinsulinemic male rats. Administration of a physiological dose of thyroxine can partially reverse (to approximatley 30% of the normal control) the marked reduction (more than 90%) in the hepatic levels of .alpha.2u globulin and its mRNA during streptozotocin-induced diabetes. Estimation of newly synthesized .alpha.2u globulin RNA transcripts from the native chromatin of isolated liver nuclei by "nuclear runoff experiments" showed that thyroxine can elevate that rate of transcription of .alpha.24 globulin gene in the diabetic rat. Hypoinsulinemic diabetes is also found to be associated with an approximately 35% reduction in the thyroid hormone receptor level as compared to the normal control. The stimulatory effect of thyroxine on the synthesis of .alpha.2u globulin and its mRNA was also evident in spontaneous diabetic Wistar "BB" rats. From these studies it can be concluded that severe hypoinsulinemia can cause a decrease in thyroid hormone action at the level of specific gene expression.