Effect of natural oestrogens on tryptophan metabolism: evidence for interference of oestrogens with kynureninase
Wolf, H.; Walter, S.; Brown, R.R.; Arend, R.A.
Scandinavian Journal of Clinical and Laboratory Investigation 40(1): 15-21
1980
ISSN/ISBN: 0036-5513 DOI: 10.3109/00365518009091522Document Number: 448956
12 healthy postmenopausal women were studied in this project with a 2-fold aim--1) to investigate whether the administration of natural estrogens in physiological doses was able to induce changes in tryptophan metabolism, and 2) to investigate, by means of the kynurenine load test, whether kynureninase activity in vivo is depressed by natural estrogens. The natural estrogens ingested by the subjects were estradiol and estriol, and they were administered before and after loading doses of 9800 mcmol of L-tryptophan or 700 mcmol of L-kynurenine suffate. Then urinary excretion of metabolites of tryptophan-nicotinic acid ribonucleotide pathway, urinary excretion of 4-pyridoxic acid, and blood concentrations of estradiol and pyridoxal phosphate were measured. It was found that natural estrogens induced abnormalities of tryptophan metabolism similar to those induced by synthetic estrogen preparations; in addition, a dose-related increase in urinary excretion of metabolites of the tryptophan-nicotinic acid ribonucleotide pathway before the kynureninase step was noted. An in vivo inhibitory effect of estrogens on kynureninase was indicated by the increase in urinary excretion of these metabolites after a loading dose of 700 mcmol of L-kynurenine. This inhibition may be mediated through decreased availability of vitamin B6, the coenzyme of kynureninase, but that argument does not rule out a direct effect of estrogens on kynureninase.