Insulin and Dexamethasone Regulation of a Rat Hepatoma Messenger Ribonucleic Acid: Insulin Has a Transcriptional and a Posttranscriptional Effect*

Abstract

Experiments were conducted to investigate the actions of glucocorticoids and insulin on the induction of a specific mRNA (p33-mRNA) expressed in rat H4 hepatoma cells. Previous studies have found a 10-fold increase in this mRNA following 60 min of insulin addition. In the present study, dexamethasone (Dex) induced the cellular concentration of p33-mRNA 10- to 15-fold. This effect was time and dose dependent. The effect of Dex could be accounted for by a 10- to 15-fold increase in p33-mRNA transcription. However, insulin administration resulted in only a 3-fold increase in the transcription of p33-mRNA. The insulin induction of transcription was time and dose dependent and was blocked by the addition of .alpha.-amanitin. There was no increase in the transcription of a control gene, .beta.-tubulin, by either insulin or Dex. Neither insulin nor Dex altered the stability of p33-mRNA. Since the cellular concentration of p33-mRNA was induced to a greater extent than was transcription, insulin must be regulating at least one other step in the sequence between RNA synthesis and RNA stability.