Dataset Information

Tyrosine aminotransferase induction in hepatocytes cultured from rat foetuses treated with dexamethasone in utero.

ABSTRACT: 1. The administration of dexamethasone to foetal rats in utero does not result in the appearance of specific tyrosine aminotransferase activity even after 24 h. 2. When foetal hepatocytes are cultured in vitro from animals treated in utero with dexamethasone, significantly higher activities of specific tyrosine aminotransferase are found than in untreated controls. 3. Dexamethasone in vitro induces specific tyrosine aminotransferase in cells cultured from control animals and the effect is maximal at 10 nM in the culture medium. 4. Actinomycin D at 0.2 microgram/ml in the culture medium completely prevents the induction of activity in vitro. 5. In cultures established from animals treated with dexamethasone in utero, the increase in specific tyrosine aminotransferase activity over the control cultures is only marginally decreased in the presence of actinomycin D. 6. The results can be interpreted to mean that dexamethasone in utero stimulates the transcription of enzyme-specific mRNA, which is not rranslated until a translational block in the foetal liver is removed by the conditions of culture in vitro.

SUBMITTER: Yeoh GC

PROVIDER: S-EPMC1161092 | biostudies-other | 1979 Jun

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:We have analysed the effects of natural aliphatic polyamines on hormonal induction of tyrosine aminotransferase (TAT) in suspensions of hepatocytes isolated from adult fed rats. Glucagon or cyclic AMP derivatives (dibutyryl and 8-bromo) used alone caused a 4-5 fold increase in enzyme activity within 4h. This effect was independent of glucocorticoids, which also increased TAT activity (2.5-fold); when combined, the effects of the two inducers were additive. Spermine and putrescine totally inhibited the hormonally-mediated increase in enzyme activity when added at the onset of incubation with the inducers. Furthermore, polyamines could block the hormonal effect at any time during the course of TAT induction, with, however, a 30 min lag period, suggesting that they must enter the cells. Hepatocytes were indeed shown to take up spermine. At low external concentrations (less than 50 microM), an Na+-dependent, saturable and concentrative mechanism was predominant; at high concentrations (greater than 0.5 mM) transport occurred mainly through a non-saturable, Na+-independent mechanism, building up intracellular concentrations slightly lower than those in the medium. Dose-dependence analysis of the polyamine effect on enzyme induction indicated that half-maximal and maximal inhibition occurred with 0.75 mM- and 2.5 mM-spermine respectively, whereas 2.5mM- and 7.5 mM-putrescine were required respectively to obtain similar effects. Spermidine was much less effective and cadaverine had virtually no effect. None of the polyamines affected the rate of decay of TAT, nor did they directly or indirectly cause enzyme inactivation, indicating that a post-translational modification was unlikely to account for the polyamine effects. Similarly, these effects could not be ascribed to a non-specific inhibition of overall protein synthesis. We conclude that, in hepatocytes, polyamines (or their metabolites) directly interfere with one or several steps controlled by hormones in the synthesis of tyrosine aminotransferase.

Dataset Information

Tyrosine aminotransferase induction in hepatocytes cultured from rat foetuses treated with dexamethasone in utero.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets