Oxidative Metabolism of Estradiol

Abstract

The metabolism of the estrogenic hormone is oxidative in nature in contrast to the reductive pathway for the neutral steroid hormones. It has been postulated that estrone is the precursor of estriol on the evidence that the required ketol intermediates are normal metabolites of the estrogenic hormone (2-4). However, it is equally true that enzymatic hydroxylation of chemically unreactive methylene groups is a common feature of steroid biochemistry (5), and thus estradiol might serve as the immediate precursor of estriol with the ketols formed by subsequent oxidation. To clarify this problem we have examined the metabolism of estrone and estradiol simultaneously in the same human subject. For this purpose, estradiol labeled with tritium in ring B and estrone-16-Cl4 were dissolved together and administered intravenously to three different patients. The ratio of weight as well as isotope of the two hormones was varied in each of the studies. Urine and blood collections were obtained at successive intervals immediately after the injections and the isotopic content of the metabolites was examined after purification to radiochemical homogeneity. The results of the three studies were completely concordant. It was shown that the rate of conversion of estrone to estradiol was slow, whereas the reverse reaction was quite rapid. It seems clear that estrone rather than estradiol is the major precursor of estriol, 2-methoxyestrone, and 16-epiestriol.