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

Abstract

The effects of glucocorticoids, pregnancy, estrogens, contraceptive steroids, and androgens upon tryptophan metabolism in man are discussed. Treatment with hydrocortisone produces an increase in the urinary excretion of kynurenine, 3-hydroxykynurenine, xanthurenic acid, and 3-hydroxyanthranilic acid, which is prevented by the simultaneous administration of large doses of vitamin B₆. Pregnant women, those using estrogen-progestogen preparations for contraceptive purposes, and subjects receiving estrogens alone, all excrete elevated levels of these metabolites, although much larger quantities of xanthurenic acid are excreted than occur following single injections of hydrocortisone. The increased urinary output of N¹-methylnicotinamide in these situations is a reflection of the enhanced capacity for the biosynthesis of nicotinic acid ribonucleotide from l-tryptophan. The progestogen megestrol acetate does not alter tryptophan metabolism when used alone for ovulation control. Mesterolone, an androgenic steroid, reduces the urinary excretion of tryptophan metabolites, and impairs the response to hydrocortisone administration. [See figure in the PDF file] The possible mechanisms by which pregnancy and estrogens modify tryptophan metabolism are discussed and, in the light of evidence obtained from animal experiments, it is concluded that estrogens cause an induction of tryptophan oxygenase that is mediated via the hypothalamo-pituitary-adrenal axis. Late in pregnancy, a true vitamin B₆ deficiency is superimposed upon the hormonal effects.