REGULATION OF ARGININOSUCCINATE SYNTHETASE MESSENGER-RNA LEVEL IN RATFETAL HEPATOCYTES

Expression of the hepatic gene for argininosuccinate synthase (ASS), o ne of the key enzymes of the urea cycle, was analysed during the perin atal period in the rat. To this end, the amount of specific mRNA was m easured in the liver at various stages of development and in cultured foetal hepatocytes maintained in different hormonal conditions. The AS S mRNA was first detected in 15.5-day foetuses and its level increased concomitantly with a rise in the enzyme activity, suggesting that the appearance of the ASS activity reflects the turning on of specific ge ne transcription. This was demonstrated by run-on assay which showed a n enhanced rate of transcription of the ASS gene during the perinatal period. When foetal hepatocytes were cultured with dexamethasone, a do se-dependent increase in ASS mRNA was measured, which was completely a bolished by actinomycin D addition. The transcription rate of the gene was increased about twofold in the presence of the steroid, as measur ed by nuclear run-on assay. This transcriptional action could addition ally require a protein factor since it could be inhibited by the simul taneous addition of puromycin. Insulin or glucagon respectively repres sed or enhanced the dexamethasone-induced accumulation of ASS mRNA whe n added simultaneously with the steroid for 24 h. This developmental r egulation of the ASS mRNA by glucocorticoids, insulin and glucagon cou ld account for the modulation of the enzyme activity previously observ ed in vivo and in vitro in the foetal liver.