Insights from the structure of estrogen receptor into the evolution of estrogens: Implications for endocrine disruption
Insights from the structure of estrogen receptor into the evolution of estrogens: Implications for endocrine disruption
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DOI：
10.1016/j.bcp.2011.03.008
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发表时间：
2011-07-01
影响因子：
5.8
通讯作者：
Baker, Michael E.
中科院分区：
文献类型：
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作者：
Baker, Michael E.
在过去的十年中，由于脊椎动物进化关键部位动物基因组的测序，在了解肾上腺类固醇（醛固酮，皮质醇）和性类固醇（雌二醇，孕酮，睾酮）受体的起源和进化方面取得了重要进展。虽然雌激素受体[ER]似乎是脊椎动物类固醇受体的祖先，雌二醇[E2]是脊椎动物ER的生理配体，但ER的祖先配体的身份仍然未知。在这里，使用E2和其他化学物质的人ER α的晶体结构分析和27-羟基胆固醇和5-雄甾烯-3 β，17 β-二醇的人ER α的3D模型，我提出一种或多种Delta S类固醇是ER的祖先配体，E2后来演变为典型的雌激素。在饱和A环的C3处具有β-羟基的化学物质可以作为雌激素和脊椎动物ER的构象灵活性的证据可以解释通过结合脊椎动物ER来破坏雌激素反应的合成化学物质的多样性。(C)2011 Elsevier Inc. All rights reserved.
In the last decade, there has been important progress in understanding the origins and evolution of receptors for adrenal steroids (aldosterone, cortisol) and sex steroids (estradiol, progesterone, testosterone) due to the sequencing of genomes from animals that are at key sites in vertebrate evolution. Although the estrogen receptor [ER] appears to be the ancestral vertebrate steroid receptor and estradiol [E2] is the physiological ligand for vertebrate ERs, the identity of the ancestral ligand(s) for the ER remains unknown. Here, using an analysis of crystal structures of human ER alpha with E2 and other chemicals and 3D models of human ER alpha with 27-hydroxycholesterol and 5-androsten-3 beta,17 beta-diol, I propose that one or more Delta S steroids were the ancestral ligands for the ER, with E2 evolving later as the canonical estrogen. The evidence that chemicals with a beta-hydroxy at C3 in a saturated A ring can act as estrogens and the conformational flexibility of the vertebrate ER can explain the diversity of synthetic chemicals that disrupt estrogen responses by binding to vertebrate ERs. (C) 2011 Elsevier Inc. All rights reserved.