Regulation of expression of the messenger ribonucleic acid encoding the cytosolic form of phosphoenolpyruvate carboxykinase in liver and small intestine of lactating rats.

The content of P-enolpyruvate carboxykinase enzyme mRNA (mRNA(PEPCK)) in the liver and small intestine changes in a coordinate way at various stages of pregnancy, lactation, and weaning periods of rats. On the ninth day of lactation, the accumulation of mRNA(PEPCK) in the liver and small intestine was 82% and 152%, respectively, compared with that in starved control rats. After 18 h of induced weaning, both tissues presented residual levels of mRNA(PEPCK). However, after 60 h of induced weaning, the accumulation of mRNA(PEPCK) increased to 60% in the liver and 76% in the small intestine compared with that in starved control rats. Adrenalectomy and bromocriptine-induced hypoprolactinemia decreased the content of this mRNA in the liver of lactating rats, while diabetes increased it. PEPCK gene transcription, determined in isolated nuclei, was 2.4-fold higher in the liver of lactating rats than in hypoprolactinemic animals, but 3.7-fold lower than that in starved animals. These results suggest that the mRNA(PEPCK) accumulation observed in the liver of lactating rats must be due to an increase in both transcription rate and messenger stabilization. PRL added to primary culture of hepatocytes obtained from lactating rats caused a dose-dependent increase in the level of mRNA(PEPCK) and mRNAc-myc. Therefore, the high PEPCK activity reported during lactation is due to increased amounts of mRNA(PEPCK), which, in turn, is due to a coordinated response at transcriptional and posttranscriptional levels, where PRL seems to play an important role.