期刊
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
卷 184, 期 -, 页码 29-37出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2018.07.001
关键词
Estrogen receptor; 5 alpha-Androstanediol; Delta 5-Androstenediol; 27-Hydroxycholesterol; Bisphenol A; Amphioxus; Estrogen receptor evolution
资金
- [3096]
Many actions of estradiol (E2), the principal physiological estrogen in vertebrates, are mediated by estrogen receptor-alpha (ER alpha) and ER beta. An important physiological feature of vertebrate ERs is their promiscuous response to several physiological steroids, including estradiol (E2), Delta(5)-androstenediol, 5 alpha-androstanediol, and 27-hydroxycholesterol. A novel structural characteristic of Delta(5)-androstenediol, 5 alpha-androstanediol, and 27-hydroxycholesterol is the presence of a C19 methyl group, which precludes the presence of an aromatic A ring with a C3 phenolic group that is a defining property of E2. The structural diversity of these estrogens can explain the response of the ER to synthetic chemicals such as bisphenol A and DDT, which disrupt estrogen physiology in vertebrates, and the estrogenic activity of a variety of plant-derived chemicals such as genistein, coumestrol, and resveratrol. Diversity in the A ring of physiological estrogens also expands potential structures of industrial chemicals that can act as endocrine disruptors. Compared to E2, synthesis of 27-hydroxycholesterol and Delta(5)-androstenediol is simpler, leading us, based on parsimony, to propose that one or both of these steroids or a related metabolite was a physiological estrogen early in the evolution of the ER, with E2 assuming this role later as the canonical estrogen. In addition to the well-studied role of the ER in reproductive physiology, the ER also is an important transcription factor in non-reproductive tissues such as the cardiovascular system, kidney, bone, and brain. Some of these ER actions in non-reproductive tissues appeared early in vertebrate evolution, long before the emergence of mammals.
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