Role of enzymes in homeostasts—VI. Effect of triamcinolone and other steroids on enzymes involved in gluconeogenesis

Abstract

In view of the reports that adrenocorticosteroids induced de novo synthesis of enzymes involved in gluconeogenesis, systematic studies were carried out to compare the potency of the various steroids and to establish the smallest dose necessary and shortest time required to detect enzyme synthesis for the key hepatic gluconeogenic enzymes, glucose 6-phosphatase and fructose 1,6-diphosphatase. The potency of triamcinolone, cortisone, hydrocortisone, and methylprednisolone (Medrol) as inducers of the gluconeogenic enzymes was compared in a 3-day injection schedule in rats and it was found that triamcinolone was the most effective inducer. Dose-response studies showed that daily injections of 10 mg of cortisone i.m. for 5 days or 1 mg of triamcinolone i.p. for 3 days achieved the highest increases in hepatic enzyme activities and nitrogen and glycogen content. In an effort to achieve a more rapid induction in enzyme synthesis cortisone and triamcinolone (25 mg/100 g) were injected i.p. Both steroids brought about a rapid rise in fructose 1,6-diphosphatase activity (128–145%) in 4–6 hr. Only triamcinolone, however, was capable of causing a significant increase in glucose 6-phosphatase activity during the same period. Further dose-response studies with triamcinolone revealed that a single i.p. dose of 0–25 mg/100 g was sufficient to induce statistically significant increases in hepatic glucose 6-phosphatase (140%) and in fructose 1,6-diphosphatase (159%) activity in 24 hr. A dose of 0.5 mg was capable of causing a statistically significant rise (117–121%,) in hepatic gluconeogenic enzyme activity in 6 hr. Since rapid increases in liver glucose 6-phosphatase and fructose 1,6-diphosphatase activity can be induced by triamcinolone administration, it appears that the mechanism of effect of the gluconeogenic corticosteroid hormones at the molecular level entails an early stepping up of the rate of synthesis of these key gluconeogenic enzymes.