Primary activation of cytosolic phosphoenolpyruvate carboxykinase gene in fetal rat liver and the biogenesis of its mRNA.

The primary appearance of phosphoenolpyruvate (P-pyruvate) carboxykinase RNA transcripts in fetal liver was induced by a number of different stimulii . This may occur as rapidly as an hour after injection in utero of N6,O2'-dibutyryl-adenosine 3',5'-monophosphate (Bt2cAMP) to fetuses, suggesting that all stimulii predominantly affect activation of the P-pyruvate carboxykinase gene. Bt2cAMP treatment induces the appearance of the enzyme RNA transcripts, predominantly of the mature type in the cytoplasm. However, insulin deficiency by streptozotocin treatment causes the appearance of large-size as well as mature mRNA in the nucleus, in addition to the appearance of P-pyruvate carboxykinase mRNA in the cytoplasm. Insulin treatment of such diabetic fetuses, prior to causing the disappearance of P-pyruvate carboxykinase mRNA, reduces nuclear transcripts but increases the abundance of mature cytoplasmic enzyme mRNA. Bt2cAMP treatment of insulin-deficient fetuses causes an additive effect, increasing the abundance of not only the mature but the large P-pyruvate carboxykinase RNA transcripts as well. The results are best interpreted as insulin acting both to inhibit transcription of and accelerate post-transcriptional processes affecting P-pyruvate carboxykinase RNA.