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Identification of 16 alpha-hydroxy-estrone as a metabolite of estriol.

During a study on the uptake and retention of estrogens by uterine tissues in postmenopausal women, evidence was obtained of the presence of a metabolite of estriol, tentatively identified as 16 alpha-hydroxy-estrone (16-OHE1). In view of the recent hypothesis concerning the role of 16-OHE1 as a risk marker for breast cancer, attempts were made to establish the identity of the metabolite. After infusions with labelled estriol, radioactive material with chromatographic properties of 16-OHE1 was observed; insufficient material was obtained for micro-recrystallization. After oral administration of estriol, myometrial tissue was extracted, then purified by chromatography and the appropriate fraction was analyzed by gas chromatography-mass spectrometry, monitored at 3 specific mass units. In the women receiving estriol the presence of 16-OHE1 could be unequivocally demonstrated, the concentrations in the myometrium being 6 and 18 ng/g tissue, whereas less than 0.2 ng/g was found in an untreated patient. This identification of 16-OHE1 does not support the hypothesis about its prominent role in human breast cancer. Additional investigations will be necessary to clarify its role in the process of stimulation of estrogen-sensitive tissues under physiological conditions and after exogenous administration of estriol.