title: Androgen signaling in decidualizing human endometrial stromal cells enhances resistance to oxidative stress.
abstract: OBJECTIVE
  To investigate the effect of androgens on the expression of genes involved in oxidative stress resistance in decidualized human endometrial stromal cells (HESCs).
  
  
  METHODS
  In vitro experiment.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Premenopausal women undergoing hysterectomy for uterine fibroids.
  
  
  METHODS
  Human endometrial stromal cells isolated from hysterectomy specimens were decidualized with 8-bromo-cyclic adenosine monophosphate (8-br-cAMP) and P in the presence or absence of dihydrotestosterone (DHT) at various concentrations. Hydrogen peroxide was used as a source of reactive oxygen species.
  
  
  METHODS
  Prolactin secretion, apoptosis, FOXO1, and the free radical scavengers superoxide dismutase 2 (SOD2) and SOD1 protein expression.
  
  
  RESULTS
  Prolactin production was induced in HESCs in response to 8-br-cAMP and P. Dihydrotestosterone further enhanced the secretion of PRL in cells treated with 8-br-cAMP plus P. The effect of DHT was blocked by the antiandrogen flutamide. Dihydrotestosterone enhanced resistance to oxidative stress-induced apoptosis on decidualized HESCs. Moreover, DHT enhanced FOXO1 expression in parallel with increased SOD2 protein but not with SOD1.
  
  
  CONCLUSIONS
  Androgens might play a critical role in the decidualization process at the time of embryo implantation and trophoblast invasion by promoting resistance to oxidative stress.
authors.affiliation: Department of Obstetrics and Gynecology, Saitama Medical University, Moroyama, Iruma-gun, Saitama, Japan. kajihara@saitama-med.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kajihara
authors.forename: Hideno
authors.initials: H
authors.lastname: Tochigi
authors.forename: Japarath
authors.initials: J
authors.lastname: Prechapanich
authors.forename: Satomi
authors.initials: S
authors.lastname: Uchino
authors.forename: Atsuo
authors.initials: A
authors.lastname: Itakura
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Brosens
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishihara
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000328:Adult; D000726:Androgen Antagonists / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D013196:Dihydrotestosterone / Q000378:metabolism* / Q000494:pharmacology; D004717:Endometrium / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007044:Hysterectomy; D007889:Leiomyoma / Q000601:surgery; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017697:Premenopause; D011388:Prolactin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D017154:Stromal Cells / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014594:Uterine Neoplasms / Q000601:surgery; D000099156:Superoxide Dismutase 2
chemical_list: D015124:8-Bromo Cyclic Adenosine Monophosphate; D000726:Androgen Antagonists; D013196:Dihydrotestosterone; D005485:Flutamide; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D011388:Prolactin; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C085126:FOXO1 protein, human; C000606290:SOD1 protein, human