Differential regulation of estrogen receptor (ER)α and ERβ in primate mammary gland
Differential regulation of estrogen receptor (ER)α and ERβ in primate mammary gland
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DOI：
10.1210/jc.2004-0861
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发表时间：
2005-01-01
影响因子：
5.8
通讯作者：
Gustafsson, JÅ
中科院分区：
文献类型：
--
作者：
Cheng, GJ;Li, Y;Gustafsson, JÅ
雌激素，主要是雌二醇(E2)和孕酮(P)对乳房的生长和分化是必不可少的，但它们在乳腺癌中的作用仍有很大争议。要了解E2和P如何影响细胞的增殖和分化，了解它们的受体是如何调节的是至关重要的。由于组织可获得性有限，人们对两种雌激素受体(ERα和ERβ)和两种孕激素受体亚型(PR-A和PR-B)在正常乳腺中的调节知之甚少。我们所知道的来自啮齿动物的研究，而这些研究并不总是与人类的乳房相关。我们现在报道了恒河猴乳腺中性激素受体在月经周期、妊娠和哺乳期的调节以及这些受体与增殖的关系。我们发现，当E2水平增加和细胞进入细胞周期时，ERpha而不是ERbeta被下调。PR-B在增殖细胞中表达，而PR-A不表达。因此，在正常情况下，乳房中ERα和ERβ的比率取决于血浆中E2的浓度。ERα的高表达(在绝经后妇女中发生)是对E2丢失的正常反应，表明非增殖细胞。随着选择性受体配体的出现，它们将有助于描述这些受体的功能。
Estrogen, mainly estradiol (E2), and progesterone ( P) are essential for the growth and differentiation of the breast, but their roles in breast cancer are highly debated. To understand how E2 and P influence cell proliferation and differentiation, it is essential to know how their receptors are regulated. Because of limited tissue availability, little is known about regulation of the two estrogen receptors (ERalpha and ERbeta) and the two progesterone receptor isoforms (PR-A and PR-B) in the normal human breast. What we know comes from rodent studies, which are not always pertinent for the human breast. We report now on regulation of gonadal hormone receptors during the menstrual cycle, pregnancy, and lactation in rhesus monkey mammary gland and on the relationship of these receptors to proliferation. We found that ERalpha but not ERbeta is down-regulated when E2 levels increase and when cells enter the cell cycle. PR-B but not PR-A is expressed in proliferating cells. Thus under normal conditions, the ratio of ERalpha to ERbeta in the breast depends on plasma concentrations of E2. Elevated expression of ERalpha (as occurs in postmenopausal women) is a normal response to loss of E2 and indicates nonproliferating cells. As selective receptor ligands become available, they will be helpful in delineation of the functions of these receptors.