Glucocorticoid induction of tryptophan oxygenase: Attenuation by intragastrically administered carbohydrates and metabolites

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In vivo tryptophan 2,3-dioxygenase (TPO) activity in male rats was estimated from the rate of production of 14CO 2 after intragastric administration of [ 14C-2]tryptophan. The synthetic glucocorticoids hydrocortisone-21-sodium succinate or Triamcinolone acetonide were injected to elevate hepatic TPO activity on an acute (1–6 hr) or chronic (24 hr) basis. Glucose, fructose, or glycerol was intragastrically intubated in doses ranging from 4 to 16 mmoles to assess their abilities to attenuate acute or chronic increases of TPO activity by these glucocorticoids. Hydrocortisone-21-sodium succinate at doses of 0, 25,and 50 mg/kg produced dose-dependent elevations of TPO. A 50 mg/kg dose produced a 3-fold elevation of enzyme activity when measured in vitro as product produced by liver homogenates and a 2-fold elevation when assessed from expired radioactie carbon dioxide from radiolabeled tryptophan in vivo. Enzyme activity measured by 14CO 2 production reached peak values in 2–3 hr and returned to baseline in 5 hr. Glucose, fructose or glycerol completely prevented the rise in conversion of [ 14C-2]tryptophan produced by hydrocortisone hemisuccinate when administered at doses of 12 or 16 mmoles 0.5 hr before the steroid. Lower doses had less effect. The potencies of the compounds in inhibiting acute increases in TPO activity produced by hydrocortisone hemisuccinate were in the order glycerol > fructose > glucose. Chronic Triamcinolone treatment elevated in vivo TPO activity by 2.5-fold and in vitro TPO activity by 5-fold. The chronic elevation of in vivo TPO by Triamcinolone could be arrested within 1 hr by an intragastric fructose load. The present finding, that acute or chronic glucocorticoid-induced increases in in vivo TPO activity were rapidly blocked by intragastric carbohydrate loads, is consistent with the view that dietary carbohydrates modulate hepatic TPO activity via feedback repression and not by a cessation of TPO enzyme synthesis.