Development of gluconeogenesis in neonatal rat liver. Effect of triamcinolone

Abstract

1. The normal development of the key enzymes of gluconeogenesis in rat liver, glucose 6-phosphatase, hexose diphosphatase, phosphopyruvate carboxylase and pyruvate carboxylase, was measured during the neonatal period. 2. Glucose 6-phosphatase, hexose diphosphatase and pyruvate carboxylase are all present in the late foetal liver, but all the enzymes show an increase in activity after birth. 3. Phosphopyruvate carboxylase is not present in liver extracts from foetal rats, but activity appears immediately after birth and increases rapidly over the first day and then more slowly to reach its maximum at the fourth postnatal day. 4. The fluorinated synthetic glucocorticoid, triamcinolone, was administered to foetal rats at various gestation times by intraperitoneal injection in utero and the animals were killed at intervals between 4 and 48hr. later. 5. The administration of triamcinolone results in slight depression of glucose 6-phosphatase, and a more significant depression of hexose diphosphatase to about one-half its normal activity in foetal rat liver. 6. Triamcinolone injection is without effect on pyruvate carboxylase activity and does not result in premature appearance of phosphopyruvate carboxylase in foetal rat liver. 7. Pyruvate kinase and aspartate amino-transferase activities in foetal rat liver are both depressed by triamcinolone treatment, whereas phosphofructokinase activity is elevated. 8. Tyrosine amino-transferase activity in foetal rat liver is markedly elevated in animals exposed to triamcinolone for 10hr. or more, but the effect is only observed in animals close to term. 9. The results are discussed in relation to mechanisms involved in the initial synthesis of tissue-specific enzymes in developing tissues, and it is concluded that glucocorticoids do not initiate the synthesis of the gluconeogenic enzymes.

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

“…The coincidence of the rapid decrease in the insulin/glucagon molar ratio at birth [6-81 and the rapid increase in the synthesis of gluconeogenic enzymes immediately afterwards [8,33], has led to much investigation into the role of glucagon and cAMP in the primary regulation of these enzymes in the developing rat liver [3,9,32,34]. Although it has been demonstrated that BtZcAMP is capable of causing the premature appearance of these enzymes [9,33,36] whereas glucocorticoids are not [lo, 331, the experimental information is far from decisive.…”

Altered Growth, Hypoglycemia, Hypoalaninemia, and Ketonemia in the Young Rat: Postnatal Consequences of Intrauterine Growth Retardation

“…During fetal life, PEPCK activity is virtually absent (1,22); its activity increases approximately 25-fold during the first 24-48 h of life (1,22,33). Pyruvate carboxylase, fructose 1,6-diphosphatase and glucose-6-phosphatase (1,22,33,34) are induced during later fetal life and their activities during neonatal life, although relatively limited compared to later life, are adequate to sustain gluconeogenesis. Thus, PEPCK is considered rate-limiting in the normal newborn rat.…”

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

“…Methods Injection of animals. Foetal animals were injected in utero as described by Yeung et al (1967). Control foetuses (201l of propylene glycol) or test foetuses (64,ug of dexamethasone in 20,1 of propylene glycol) were injected by using a 30-gauge dental needle attached by cannula tubing to an Agla syringe driven by a micrometer (Burroughs Wellcome, Beckenham, Kent, U.K.).…”