title: Differential mRNA expression profiling in ovarian endometriotic tissue with versus without leuprolide acetate treatment.
abstract: OBJECTIVE
  Leuprolide acetate, an analog of gonadotropin-releasing hormone (GnRH), regresses endometriotic tissue and reduces pain, resulting in clinical improvement upon treatment. The molecular mechanisms involved in the regression of endometriotic tissue, however, remain to be elucidated. In this study, we performed genome-wide gene expression profiling of clinical specimens of ovarian endometrioma to obtain insight into the effects of leuprolide acetate treatment.
  
  
  METHODS
  We obtained clinical samples from nine normal eutopic endometrium tissues, eight ovarian endometriotic tissues, and 12 leuprolide acetate-treated endometriotic tissues. We compared the gene expression profiles of the three groups using Affymetrix GeneChip Human genome arrays and bioinformatic analysis, including molecular concept analysis.
  
  
  RESULTS
  Leuprolide acetate-treated endometriotic tissue showed downregulated genes associated with the biological functions of steroid hormone regulation, cell proliferation, inflammation, and intracellular signaling. These genes included PTGDS, GRP, APLP2, PLTP, and FGFRL1. In contrast, genes upregulated by leuprolide acetate treatment were associated with cell growth inhibition and apoptosis. These genes included CARD11 and USP18.
  
  
  CONCLUSIONS
  These preliminary results based on GeneChip analysis suggest that leuprolide acetate treatment induces a modulation of gene expression that allows for cooperative alterations in disease state. This study gives new insight into the effects of leuprolide acetate treatment. Further investigations with quantitative reverse transcription-polymerase chain reaction and immunohistochemistry are needed to validate this study and to explore new therapeutic targets and biomarkers of endometriosis.
authors.affiliation: Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Kanagawa, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kiba
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Banno
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Yanokura
authors.affiliation: Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Kanagawa, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Asada
authors.affiliation: Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Kanagawa, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakayama
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
authors.affiliation: Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Kanagawa, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology* / Q000627:therapeutic use; D016000:Cluster Analysis; D004715:Endometriosis / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D016729:Leuprolide / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology
chemical_list: D018931:Antineoplastic Agents, Hormonal; D016729:Leuprolide
keywords: endometriosis; geneChip; leuprolide acetate