title: Endometriosis: hormone regulation and clinical consequences of chemotaxis and apoptosis.
abstract: 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 studies evaluating 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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Fernando M
authors.initials: FM
authors.lastname: Reis
authors.forename: Felice
authors.initials: F
authors.lastname: Petraglia
authors.forename: Robert N
authors.initials: RN
authors.lastname: Taylor
mesh_terms: D017209:Apoptosis; D002633:Chemotaxis; D004715:Endometriosis / Q000276:immunology / Q000378:metabolism*; D004717:Endometrium / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D004967:Estrogens / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011372:Progestins / Q000378:metabolism*; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
chemical_list: D004967:Estrogens; D016209:Interleukin-8; D016328:NF-kappa B; D011372:Progestins; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: apoptosis; chemokines; endometriosis; endometrium; hormones
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