title: In silico analysis identifies a novel role for androgens in the regulation of human endometrial apoptosis.
abstract: BACKGROUND
  The endometrium is a multicellular, steroid-responsive tissue that undergoes dynamic remodeling every menstrual cycle in preparation for implantation and, in absence of pregnancy, menstruation. Androgen receptors are present in the endometrium.
  
  
  OBJECTIVE
  The objective of the study was to investigate the impact of androgens on human endometrial stromal cells (hESC).
  
  
  METHODS
  Bioinformatics was used to identify an androgen-regulated gene set and processes associated with their function. Regulation of target genes and impact of androgens on cell function were validated using primary hESC.
  
  
  METHODS
  The study was conducted at the University Research Institute.
  
  
  METHODS
  Endometrium was collected from women with regular menses; tissues were used for recovery of cells, total mRNA, or protein and for immunohistochemistry.
  
  
  RESULTS
  A new endometrial androgen target gene set (n = 15) was identified. Bioinformatics revealed 12 of these genes interacted in one pathway and identified an association with control of cell survival. Dynamic androgen-dependent changes in expression of the gene set were detected in hESC with nine significantly down-regulated at 2 and/or 8 h. Treatment of hESC with dihydrotestosterone reduced staurosporine-induced apoptosis and cell migration/proliferation.
  
  
  CONCLUSIONS
  Rigorous in silico analysis resulted in identification of a group of androgen-regulated genes expressed in human endometrium. Pathway analysis and functional assays suggest androgen-dependent changes in gene expression may have a significant impact on stromal cell proliferation, migration, and survival. These data provide the platform for further studies on the role of circulatory or local androgens in the regulation of endometrial function and identify androgens as candidates in the pathogenesis of common endometrial disorders including polycystic ovarian syndrome, cancer, and endometriosis.
authors.affiliation: Medical Research Council Centre for Reproductive Health, The University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH164TJ, United Kingdom.
authors.forename: Elaine
authors.initials: E
authors.lastname: Marshall
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Lowrey
authors.forename: Sheila
authors.initials: S
authors.lastname: MacPherson
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Maybin
authors.forename: Frances
authors.initials: F
authors.lastname: Collins
authors.forename: Hilary O D
authors.initials: HO
authors.lastname: Critchley
authors.forename: Philippa T K
authors.initials: PT
authors.lastname: Saunders
mesh_terms: D000328:Adult; D000728:Androgens / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D011401:Promoter Regions, Genetic; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000728:Androgens; D011944:Receptors, Androgen