Effect of Triamcinolone on Renal and Hepatic Phosphoenolpyruvate Carboxykinase in the Newborn Rat

Abstract

The effects of triamcinolone on renal and hepatic phosphoenolpyruvate carboxykinase activity in the developing rat were investigated. The hormone induced increases in pre-existing enzyme activity of both tissues in fetal and neonatal rats, yet did not cause the primary appearance of phosphoenolpyruvate carboxykinase activity in utero.Neonatal hepatic phosphoenolpyruvate carboxykinase activity was increased 2 -3-fold by triamcinolone from the 3rd to the 15th postnatal day. This was shown to be additive to the effect of BtzcAMP on enzyme activity. The increases in phosphoenolpyruvate carboxykinase activity were demonstrated to be due to increased synthesis of the enzyme, which was accompanied by a proportionate increase in the amount of functional phosphoenolpyruvate carboxykinase mRNA, as measured by the polyribosomal and poly(A)-containing RNA directed cell-free synthesis of the enzyme.The demonstration of a triamcinolone effect on kidney and liver phosphoenolpyruvate carboxykinase activity in fetal and neonatal rats provides support for a possible role of glucocorticoids in the regulation of phosphoenolpyruvate carboxykinase activity during development.

Control of the Activity of Phosphoertolpyruvate Carboxykinase and the Level of ItsmRNA in Livers of Newborn Rats

“…The parallel relative decrease (about fourfold) in the abundance and translatable enzyme mRNA by insulin treatment of adult diabetic rats, indicates that alterations in the translatable mRNA represent quantitative changes. This may be extended to neontates exhibiting similar increases in the abundance (present study) and translatable mRNA (previous study) [1] after glucocorticoid treatment. The consistent yield of poly(A)-rich R N A in neonates (60 -80 pg/g liver) irrespective of treatment, implies that the observed changes in the relative abundance of P-pyruvate carboxykinase mRNA are quantitatively significant.…”

“…RNA from post-mitochondria1 liver supernatant of adult rats (cytosol RNA) was extracted according to Nienhuis et al [22] as previously described by Reshef et al and Mencher and Reshef [1,23]. Isolation of poly(A)-rich RNA by oligo(dT)-cellulose chromatography, translation in wheat germ lysates and determination of P-pyruvate carboxykinase mRNA translatable activity was as previously described [I].…”

Role of the Isoforms of CCAAT/Enhancer-binding Protein in the Initiation of Phosphoenolpyruvate Carboxykinase (GTP) Gene Transcription at Birth

“…Although this gene is not expressed in the fetal liver and appears at birth (18), it can be prematurely activated by increasing the glucagon/insulin ratio to a state that is similar to that which prevails at birth (19). It is possible to cause the premature activation of PEPCK gene expression by injecting fetuses in utero with Bt 2 cAMP or by administering streptozotocin, which causes insulin deficiency (20,21). Fur-thermore, the chromatin conformation of the PEPCK gene in the liver undergoes a gradual transition from a "compact" conformation on day 19 of gestation to an "open" conformation just prior to the initiation of its transcription at birth (18).…”

Cycloheximide and pactamycin inhibit the rapid decrease in translatable mRNA activity of P‐enolpyruvate carboxykinase (GTP)

“…Isolation of poly(A)+ RNA from postmitochondrial liver supernatants 143, translation in wheat germ lysates and determination of P-enolpyruvate carboxykinase mRNA translatable activity, were performed as in [3,6,7]. Preparation of wheat germ lysates was as in [8,9].…”