Hormonal regulation of lipogenic enzymes in XXXX embryo hepatocytes in culture. Thyroid hormone and glucagon regulate malic enzyme mRNA level at post-transcriptional steps.

@entity5808 @entity4316 @entity1573 @entity1954 @entity17547
Mechanisms involved in stimulation of the synthesis of malic enzyme by @entity17547 and @entity1954 and in inhibition of synthesis by glucagon have been investigated by assessing levels and rates of synthesis of malic enzyme mRNA in @entity1573 embryo hepatocytes in culture. @entity17547 alone had no effect on the level of malic enzyme mRNA, whereas @entity1954 by itself caused a 7-fold increase. @entity17547 plus @entity1954 caused an 11-fold increase. Glucagon caused a 93% decrease in the accumulation of malic enzyme mRNA caused by @entity17547 plus @entity1954 . Although the relative changes in mRNA level are smaller in magnitude, they are qualitatively similar to the effects of these hormones on synthesis of malic enzyme, suggesting that control is exerted primarily at pretranslational steps. After addition of @entity1954 , malic enzyme mRNA accumulated with sigmoidal kinetics, approaching a new steady state at 36-48 h after adding hormone. @entity5808 , an inhibitor of protein synthesis, blocked the effect of @entity1954 if added 30 min prior to the hormone and inhibited further accumulation of malic enzyme mRNA if added 24 h after @entity1954 . However, @entity5808 had no effect on the level of beta-tubulin mRNA (t1/2 = 3-5 h), suggesting that the effect of @entity1954 on malic enzyme mRNA required synthesis of a peptide. @entity1954 increased transcription of the malic enzyme gene by 2-fold and level of its mRNA by 11-14-fold, indicating regulation is primarily at a post-transcriptional step. Glucagon caused malic enzyme mRNA to decay with a half-life of 1.5 h, whereas alpha-amanitin or @entity4316 , inhibitors of transcription, caused the mRNA to decay with a half-life of 8-11 h. The effect of glucagon was entirely post-transcriptional because the hormone had no effect on transcription. Taken together, these results suggest a model in which @entity1954 regulates production of a peptide that stabilizes malic enzyme transcripts in the cytoplasm and/or nucleus. Glucagon may inhibit activity of the peptide induced by @entity1954 .
