科研之友
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摘要
Oxidative metabolism of estrogens is an important feature in liver and some non-hepatic tissues. In initial studies on estrogen metabolism in tissues from the reproductive tract of the stallion, where testicular estrogen secretion is remarkably high, a prominent radiolabeled product from [H-3]-estrone (El) was noted on chromatography; it had a retention time (Rt) between 17 beta-estradiol (E2) and El. Unexpectedly, when non-radiolabeled El was the substrate no UV absorption at 280 nm was seen at the Rt for the [H-3] labeled product suggesting a non-aromatic ring A. The following efforts were made to reveal more about the nature of the "unknown" compound. Reduction and acetylation showed, separately, the presence of a single keto and hydroxyl group. Exposure to acid gave a single radiolabeled peak with Rt of 6 alpha-hydroxy-E1 suggesting the presence of a third molecule of oxygen. Mass spectrometry with limited material was inconclusive but supportive for a formula of C18H22O3. Thus, an epoxide involving the aromatic ring of E1- is suggested as a labile intermediate in the formation of the "unknown" metabolite. Estrogen epoxides as labile, reactive intermediates have been considered as potential precursors of the 2-and 4-hydroxy catechol estrogens with implications in breast cancer [Soloway, 2007]. Because of the association of the "unknown" metabolite with 6 alpha-hydroxy-El, the structural form proposed for the stable epoxide is that for 5 alpha,6 alpha-epoxy"estrone. This represents an alternative to the production of the 2-and 4-hydtoxycatechol estrogens. The broad range in normal tissues where the "unknown" compound was shown to be a persistent metabolite (e.g. mouse mammary glands, ovary, uterus, brain, muscle, equine conceptus, stallion and domestic boar reproductive tracts) suggests more general biological implications.
- 出版日期2017-3
