Effect of hydrocortisone on the expression of mitochondrial genes in the liver of normal and alloxan diabetic rats.

The incorporation of 14C-orotic acid into mitochondrial RNA from the liver of alloxan diabetic (AD) rats was increased after a single or repeated administration of hydrocortisone (HC; 5 mg kg-1). while the increase in normal animals was much less. The activity of RNA-polymerase in isolated mitochondria was also considerably increased in AD rats after HC administration, but this was not related to any changes of mitochondrial membrane permeability for precursors. Electrophoretic analysis of total and poly(A)-containing RNA did not show any substantial changes in liver mitochondrial RNA of AD rats treated with HC. No changes in the transcription of liver mitochondrial DNA from intact, AD or AD plus HC treated rats were found after the hybridization of mitochondrial RNA with a rat mitochondrial DNA or DNA from recombinant plasmids, containing inserts of restriction fragments of mitochondrial DNA. In addition, an increase in the rate of protein synthesis was observed after a repeated administration of HC to intact animals, while that in AD rats was decreased and started to increase only after a single administration of HC. In contrast, after a repeated administration of HC the rate of protein synthesis was decreased. It was concluded that the mechanism of RNA and protein biosynthesis in liver mitochondria of AD rats is much more sensitive to the action of glucocorticoids as compared to intact animals and that the biosynthesis of all populations of mitochondrial RNA in the liver of AD rats is increased after HC treatment in a similar degree, the quality of mitochondrial gene expression being not changed.