Excretion of tryptophan metabolites as affected by pregnancy, contraceptive steroids, and steroid hormones

Abstract

To assess the effect of pregnancy contraceptive steroids and steroid hormones on tryptophan metabolites the urinary excretion of intermediates along the tryptophan-nicotinic acid ribonucleotide pathway were studied in both rats and human beings. Tryptophan oxygenase is the rate-limiting enzyme of the tryptophan-nicotinic acid ribonucleotide pathway. A correlation has been established between tryptophan oxygenase activity in the human liver and the level of kynurenine in the urine after an oral dose of tryptophan hydrocortisone treatment increases excretion levels of kynurenine 3 hydroxykynurenine xanthurenic acid and 3 hydroxyanthranilic acid. Such elevated excretion levels can be prohibited by administration of vitamin-B-6. During pregnancy elevated levels of the previously mentioned metabolites occur. This condition is a result of: 1) a deficiency of vitamin-B-6 due to the demands of the fetus and 2) throughout pregnancy the promotion of tryptophan metabolism along the pathway due to endocrine changes. Elevated levels of metabolite excretion occur during the time of ovulation. Women using estrogen-progestogen oral contraceptives and those receiving estrogen alone experienced higher levels of the metabolites. Those receiving the progestogen megestrol acetate alone did not experience higher levels of the metabolites either. The androgen Mesterolone reduced the excretion of tryptophan metabolites and interfered with their response to hydrocortisone administration. The mechanism by which pregnancy and estrogen modify tryptophan metabolism is due to the fact that estrogens whether synthetic of natural cause an induction of tryptophan oxygenase that is mediated via the hypothalamo-pituitary-adrenal axis.