Effects of Administration of Hydrocortisone, Actinomycin D and Puromycin on Carbamoylphosphate Synthetase-I and Ornithine Carbamoyltransferase Activities in Fetal Rat Liver

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.

Effects of Corticosteroids and Pancreatic Hormones on Carbamyl Phosphate Synthetase-I and Ornithine Transcarbamylase Activities in Fetal Rat Liver

“…Consequently, the hormone might act by two different ways on enzyme activity: directly by increasing enzyme synthesis and probably indirectly by facilitating the inhibi tory effect of insulin on enzyme activity. This hypothesis is consistent with our previous findings [6]: glucocorticoid supply partially overcomes the paradoxical effect of actinomycin D on enzyme activity. Since the stim ulatory effect of the antibiotic on OTC activ ity is associated with a decrease in insulincmia, glucocorticostcroids and the high level in fetal insulinentia [3,18] might act as inhib itory factors on enzyme development, sug gesting a permissive effect of glucocorticosteroids on insulin action in vivo.…”

“…Our ear lier studies showed that the activities of CPS-I and OTC are low in the fetus and increase rapidly after birth [4], We also reported that both activities are affected by the deprivation of glucocorticoids during the late fetal period [5]. Moreover, a hydrocortisone acetate sup ply to intact fetuses increased the level of CPS-I activity 3 days later, while OTC activ ity exhibited a paradoxical increase after an actinomycin D supply [6]. In further experi ments, we found that the inhibitory effect of glucose on postnatal increase in OTC activity might be associated with the resulting in crease in insulinemia [7].…”

“…After two successive centrifugations for 15 min at 4,000 g at 4 °C, the enzyme activity was assayed on the supernatant solution according to the method of Brown and Cohen [1] with some modifica tions as previously described [6]. A unit of enzyme was the amount which catalyzed the production of 1 pmol citrulline/h/g liver at 37 °C under assay condi tions.…”

Disproportionate Growth of Organs and Body Weight following Glucocorticoid Treatment of the Rat Fetus

“…Even during the fetal period, however, glucocorticoids may have both stimulatory and inhibitory influences in the liver. For example, glucocorticoid suppresses amylo-l,6-glucosidase activity in fetal rat liver [57] and inhibits DNA synthesis in the liver of weanling rats [24], but in low doses enhances the activity of carbamoylphosphate synthetase-I [22] and conversion of T4 to T3 [61] in the fetal liver. The weanling rat has marked recuperative powers after glucocorticoid treatment as shown by increases in liver DNA polymerase activity [25] and ornithine decarboxylase [20], and complete recovery of DNA content by 8 days of recovery [25].…”

Postnatal Changes in Carbamylphosphate Synthetase-I and Ornithine Transcarbamylase Activities after Normal Birth, Premature Delivery and Prolonged Gestation in Rat Liver: Effects of Actinomycin D and Glucose

“…Freshly excised livers were imme diately weighed and homogenized in 0.1% A'-cetyl-N,N,N-trimethylammonium bromid (CTB) (4) (Merck, Darmstadt) in the ratio 1 g liver to 7 ml o f C T B for the assay of carbamylphosphate synthetase-I and orni thine transcarbamylase. After two successive centri fugations for 15 min at 4,000 g at 5 °C , the enzymatic activities were assayed on the supernatant solution according to the method o f Brown and Cohen (4) with some modifications as previously described (11). Enzyme Unit.…”