Department of Obstetrics and Gynecology, University of Minas Gerais, Belo Horizonte, Brazil.
Hum Reprod Update. 2013 Jul-Aug;19(4):406-18. doi: 10.1093/humupd/dmt010. Epub 2013 Mar 28.
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.
We searched Pubmed for items published in English between September 1991 and September 2011 and selected the studies evaluating the effects of hormones on chemokines or apoptosis in normal human endometrium and endometriosis.
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 by local chemokine production and to reinforce mechanisms of cell survival mediated by extracellular signal-regulated kinases and Bcl-2. The main effect 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-κB.
Estrogens and progestogens modulate chemotaxis and apoptosis in human endometrium and endometriotic cells and tissues. 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.
趋化因子募集免疫细胞和调控子宫内膜细胞凋亡是子宫内膜异位症生物学的关键方面。在这里，我们回顾了局部（旁分泌）和全身激素（内分泌）对这两个特定但高度相关现象的调节。
我们在 Pubmed 上搜索了 1991 年 9 月至 2011 年 9 月期间以英文发表的项目，并选择了评估激素对正常人类子宫内膜和子宫内膜异位症中趋化因子或细胞凋亡影响的研究。
雌二醇对子宫内膜细胞具有促炎和抗凋亡作用，而这些作用在子宫内膜异位症患者中似乎更为明显。在这些患者中，生理雌二醇浓度能够诱导局部趋化因子产生介导的增强炎症反应，并增强细胞生存机制，这些机制由细胞外信号调节激酶和 Bcl-2 介导。孕激素的主要作用是抑制基质细胞中白细胞介素-8 和其他趋化因子的产生，无论是在位还是异位子宫内膜。孕激素还通过抑制 Bcl-2 和核因子-κB 有效诱导子宫内膜和子宫内膜异位细胞凋亡。
雌激素和孕激素调节人类子宫内膜和子宫内膜异位细胞和组织的趋化性和凋亡。这些内分泌和旁分泌途径在子宫内膜异位症患者中失调，导致炎症反应、异常组织重塑、治疗耐药性和疾病持续存在。最终，它们促进了粘连形成以及盆腔疼痛和不孕等临床症状的出现。对涉及的分子机制的更详细了解将为诊断和治疗子宫内膜异位症的新药理学策略提供新的机会。
