POST-TRANSCRIPTIONAL REGULATION OF 3-HYDROXY-3-METHYLGLUTARYL-COA REDUCTASE MESSENGER-RNA IN RAT-LIVER - GLUCOCORTICOIDS BLOCK THE STABILIZATION CAUSED BY THYROID-HORMONES

  • 5 January 1989
    • journal article
    • research article
    • Vol. 264  (1) , 569-573
Abstract
Administration of dexamethasone to hypophysectomized rats treated with thyroid hormones blocked the increase in hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase mRNA and enzyme activity which occurred in response to thyroid hormone treatment. The rate of transcription of the rat liver HMG-CoA reductase gene measured by "run-on" assays in isolated nuclei was not diminished by dexamethasone. The half-life of HMG-CoA reductase mRNA was decreased from 12-15 to 2-3 h by dexamethasone treatment of hypophysectomized rats fed thyroid powder. Adrenalectomy caused the half-life of HMG-CoA reductase mRNA to increase from 3 to 10 h, suggesting that endogenous glucocorticoids also regulate reductase mRNA stability. Reductase mRNA levels were increased only 5-fold in thyroidectomized rats fed thyroid powder compared to a 20- to 40-fold increase in similarly treated hypophysectomized rats. In thyroidectomized rats, reductase mRNA had a half-life of only 1.5 h. Thyroid hormone treatment increased this to 4.5 h, significantly less than that of similarly treated hypophysectomized rats. Hydrocortisone, like dexamethasone, lowered reductase mRNA levels, but the biologically inactive analogue epihydrocortisone did not affect reductase mRNA or activity. These results suggest that glucocorticoids decrease the abundance of HMG-CoA reductase mRNA by stimulating its degradation.

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