Effects of oestrogen administration on vitamin B 6 and tryptophan metabolism in the rat

Abstract

1.In order to assess the effects of oestrogens on the metabolism of tryptophan and vitamin B 6 , ovariectomized rats have been maintained on diets providing known amounts of tryptophan, nicotinamide and vitamin B 6 . They received oestrone sulphate. 210μg/kg body-wt per d, either incorporated in the diet for 8 weeks, or by daily intraperitoneal injection for periods of 1–3 d. 2. Oestrone sulphate administration caused a slight reduction in the concentration of pyridoxal phosphate in plasma. It had no effect on the concentration of pyridoxal phosphate in liver or kidney, the urinary excretion of 4-pyridoxic acid, the activation of erythrocyte aspartate aminotransferase (L-aspartate:2-oxo-glutarate aminotransferase, EC 2.6.1.1)by incubation with added pyridoxal phosphate, or the activity of pyridoxal oxidase (aldehyde:oxygen oxido-reductase, EC 1.2.3.1) in the liver. 3. Oestrone sulphate administration caused an increase in the urinary excretion of kynurenine and a reduction in the activity of liver kynureninase (L-kynurenine hydrolase, EC 3.7.1.3), It had no effect on the urinary excretion of N 1 -methyl nicotinamide or the concentrations of nicotinamide nucleotides in blood, liver or kidney. 4. There was a considerable excess of the apoenzyme of kynureninase in the liver. Incubation of liver homogenates with added pyridoxal phosphate led to a 4- to 5-fold increasein activity. 5. We conclude that there is no evidence of any significant effect of oestrogens on vitamin B 6 . It is suggested that abnormalities of tryptophan metabolism in women receiving oestrogens. which have been widely attributedto drug-induced vitamin B 6 depletion, can be accounted for by inhibition of kynureninase by oestrogen metabolites.