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.
van Haaften
M
M
Department of Endocrinology, Academisch Ziekenhuis, Utrecht, The Netherlands.
Donker
G H
GH
Tas
A A
AA
Gramberg
L G
LG
Blankenstein
M A
MA
Thijssen
J H
JH
D001711:Biotransformation; D004964:Estriol / Q000378:metabolism*; D004970:Estrone / Q000031:analogs & derivatives*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006894:Hydroxyestrones / Q000302:isolation & purification*; D007044:Hysterectomy; D009215:Myometrium / Q000378:metabolism*
D006894:Hydroxyestrones; C026702:16-hydroxyestrone; D004970:Estrone; D004964:Estriol