Endometriosis: hormone regulation and clinical consequences of chemotaxis and apoptosis
Endometriosis: hormone regulation and clinical consequences of chemotaxis and apoptosis
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DOI：
10.1093/humupd/dmt010
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发表时间：
2013-07-01
影响因子：
13.3
通讯作者：
Taylor, Robert N.
中科院分区：
文献类型：
--
作者：
Reis, Fernando M.;Petraglia, Felice;Taylor, Robert N.
背景：趋化因子对免疫细胞的募集和对子宫内膜细胞凋亡的调节是子宫内膜异位症生物学的重要方面。在这里，我们回顾了局部（旁分泌）和全身激素（内分泌）调制这两个特定的，但高度相关的phenomenon.METHODS：我们检索Pubmed的项目发表在1991年9月和2011年9月之间，并选择studies evaluating the effects of hormone on chemokines or apoptosis in normal human endometrium and endometriosis.RESULTS：雌二醇在子宫内膜细胞中具有促炎和抗凋亡作用，这些作用似乎在子宫内膜异位症妇女中加重。在这些妇女中，生理雌二醇浓度能够诱导局部趋化因子产生介导的增强的炎症反应，并加强细胞外信号调节激酶和Bcl-2介导的细胞存活机制。孕激素的主要作用是抑制在位和异位子宫内膜间质细胞中的白细胞介素-8和其他趋化因子。孕激素还可通过抑制Bcl-2和核因子-κ B诱导子宫内膜和子宫内膜异位细胞凋亡。结论：雌孕激素可调节人子宫内膜和子宫内膜异位细胞及组织的趋化性和凋亡。这些内分泌和旁分泌途径在患有子宫内膜异位症的女性中受到干扰，导致炎症反应，异常组织重塑，治疗无效和疾病持续。最终，它们促进粘连形成以及盆腔疼痛和不孕症的临床症状。更详细地了解所涉及的分子机制将提供新的药理学策略，以诊断和治疗子宫内膜异位症的新机会。
BACKGROUND:The recruitment of immune cells by chemokines and the regulation of endometrial cell apoptosis are critical aspects of endometriosis biology. Here, we review the local (paracrine) and systemic hormone (endocrine) modulation of these two specific, but highly related phenomena.METHODS:We searched Pubmed for items published in English between September 1991 and September 2011 and selected the studiesevaluating the effects of hormones on chemokines or apoptosis in normal human endometrium and endometriosis.RESULTS:Estradiol has proinflammatory and antiapoptotic effects in endometrial cells, and these effects appear to be exacerbated in women with endometriosis. In these women, physiological estradiol concentrations are able to induce an enhanced inflammatory response mediated bylocal chemokine production and to reinforce mechanisms of cell survival mediated by extracellular signal-regulated kinases and Bcl-2. The maineffect of progestogens is to inhibit interleukin-8 and other chemokines in stromal cells from both eutopic and ectopic endometrium. Progesterone is also effective in inducing apoptosis in endometrial and endometriotic cells through the inhibition of Bcl-2 and nuclear factor-kappa B.CONCLUSIONS:Estrogens and progestogens modulate chemotaxis and apoptosis in human endometrium and endometriotic cells andtissues. These endocrine and paracrine pathways are perturbed in women with endometriosis, contributing to inflammatory responses, abnormal tissue remodeling, therapeutic refractoriness and disease persistence. Ultimately, they promote adhesion formation and the clinical symptoms of pelvic pain and infertility. A more detailed understanding of the molecular mechanisms involved will offer new opportunities for novel pharmacological strategies to diagnose and treat endometriosis.