Estrogen action: a historic perspective on the implications of considering alternative approaches.

Estrogen action: a historic perspective on the implications of considering alternative approaches.
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DOI:
10.1016/j.physbeh.2009.08.013
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发表时间:
2010-02-09
影响因子:
2.9
通讯作者:
Frye, Cheryl A.
Frye, Cheryl A.
中科院分区:
医学3区
文献类型:
--
作者:
Jensen, Elwood V.;Jacobson, Herbert I.;Walf, Alicia A.;Frye, Cheryl A.

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自同源雌激素受体(ER)首次报道以来的50年中,人们对雌激素(如17β-雌二醇(E2))的各种作用和机制有了很大了解。这篇专家叙述性综述简要总结了作者的观点和/或近期工作,他们一直在解决雌激素作用的不同方面,但采取了一种共同的方法,即使用替代考虑因素来深入了解具有临床相关性的机制,并为未来的研究提供信息,关于雌激素作用。他们的“十大”最喜欢的替代品,这里讨论如下。1-E2通过与不需要其酶促转化的受体结合而发挥作用。2-使用不同的抗体结合策略可以使雌激素受体(ER)更易识别。3-阻断ER而不是E2的产生可能是乳腺癌治疗的一个有用策略。4-甲胎蛋白(AFP)的分泌,而不仅仅是E2和/或孕酮的水平,可能会影响乳腺癌的风险。5-从AFP的活性位点衍生的肽可以产生与内分泌癌中的整个内源性蛋白相同的益处。6-ER亚型在身体和大脑中的差异分布可能是雌激素特异性作用的基础。7-ERβ可能足以在脑中发挥雌激素的营养作用,ERα可能是体内营养作用的主要靶点。8-ERβ可能在雄激素的营养作用中发挥作用,也可能与外周相关。9 -E2对ERβ的作用下游,可能会影响孕激素和/或雄激素的生物合成。10-可能位于ERβ下游的组蛋白和/或其他因子的变化可能是E2在脑和外周组织中的不同作用的基础。
In the 50 years since the initial reports of a cognate estrogen receptor (ER), much has been learned about the diverse effects and mechanisms of estrogens, such as 17β-estradiol (E2). This expert narrative review briefly summarizes perspectives and/or recent work of the authors, who have been addressing different aspects of estrogen action, but take a common approach of using alternative considerations to gain insight into mechanisms with clinical relevance, and inform future studies, regarding estrogen action. Their “Top Ten” favorite alternatives that are discussed herein are as follows. 1- E2 has actions by binding to a receptor that do not require its enzymatic conversion. 2- Using a different strategy for antibody binding could make the estrogen receptor (ER) more discernible. 3- Blocking ERs, rather than E2 production, may be a useful strategy for breast cancer therapy. 4- Secretion of α-fetoprotein (AFP), rather than only levels of E2 and/or progesterone, may influence breast cancer risk. 5- A peptide derived from the active site of AFP can produce the same benefits of the entire endogenous protein in endocrine cancers. 6- Differential distribution of ER subtypes in the body and brain may underlie specific effects of estrogens. 7- ERβ may be sufficient for the trophic effects of estrogen in the brain, and ERα may be the primary target of trophic effects in the body. 8- ERβ may play a role in the trophic effects of androgens, and may also be relevant in the periphery. 9 - Downstream of E2's effects at ERβ, there may be consequences for biosynthesis of progestogens and/or androgens. 10- Changes in histones and/or other factors, which may be downstream of ERβ, potentially underlie the divergent effects of E2 in the brain and peripheral tissues.
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