No abstract

Expression of the hepatic enzyme argininosuccinate lyase (ASL), one of the urea cycle enzymes, was analyzed during the perinatal period in the rat. To this end, ASL was purified, an ELISA assay was established to quantify the enzyme protein and a cDNA clone was used to measure the amount of specific mRNA in the liver in various stages of development. During the last few days of fetal life, both enzyme and hybridizable RNA were present at levels far below those measured in the fully differentiated adult liver. Just after birth, they increased rapidly and the mRNA accumulation, particularly, could result from an enhanced rate of transcription as suggested by the experiment with actinomycin D. This postnatal shift in ASL expression was also linked to adrenal activation at birth, as shown by adrenalectomy. However, the extent to which the ASL protein accumulated after birth appeared to be limited when compared to mRNA accumulation, suggesting control mechanisms at the translational level. Thus, during the perinatal period of the rat, both transcriptional and translational control might be implicated in the expression of the ASL gene.

No abstract

The administration of hydrocortisone (0.1 mg) to intact fetuses in utero on day 16.5, 17.5 and 18.5 caused a marked increase in the activity of carbamoylphosphate synthetase-I 48 h later. This increase can be abolished 48 h later by simultaneous administration of actinomycin D (2 μg). No change in the activity of ornithine carbamoyltransferase was found with administration of hydrocortisone in utero during the same period. The normal increase of the activity of carbamoylphosphate synthetase-I during the late fetal period is not abolished by administration of actinomycin D, while this treatment on day 18.5 in utero stimulates the activity of ornithine carbamoyltransferase. The normal increase of carbamoylphosphate synthetase-I activity during the late fetal period is not associated with an enzyme synthesis, while its hydrocortisone-induced increase seems to be due to an enzyme synthesis. The nature of the increase in ornithine carbamoyltransferase activity with actinomycin D remains to be identified.

The effects of corticosteroids and pancreatic hormones on two mitochondrial enzymes of ureagenesis, carbamyl phosphate synthetase-I (CPS-I) and ornithine transcarbamylase (OTC), were investigated and compared in fetal rat liver. Supplementing hydrocortisone acetate (50 μg) to 18.5-day-old fetuses significantly increased CPS-I activity (by 36%) and decreased OTC activity (by 23%). An actinomycin D supply (2 μg) to 18.5-day-old fetuses prematurely increased OTC activity and decreased fetal insulin level (by 42%). This treatment had no effect on CPS-I activity. Glucagon supply (25 μg) during the late fetal period increased both activities within 2 h, while dibutyryl-cAMP enhanced OTC activity 17 h later. These results suggested that the fetal development of CPS-I activity was under the control of corticosteroids and glucagon. In contrast, corticosteroid hormones produced an inhibitory effect on OTC activity. This might be explained by the permissive effect of corticosteroids on insulin action, since insulin might act as a repressor in utero of enzyme development. Thus, the paradoxical effect of actinomycin D on OTC activity was probably due to the decrease in fetal insulinemia.