Androgen signaling in decidualizing human endometrial stromal cells enhances resistance to oxidative stress

Fertil Steril. 2012 Jan;97(1):185-91. doi: 10.1016/j.fertnstert.2011.10.017. Epub 2011 Nov 10.

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).

Design: In vitro experiment.

Setting: University hospital.

Patient(s): Premenopausal women undergoing hysterectomy for uterine fibroids.

Intervention(s): 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.

Main outcome measure(s): Prolactin secretion, apoptosis, FOXO1, and the free radical scavengers superoxide dismutase 2 (SOD2) and SOD1 protein expression.

Result(s): 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.

Conclusion(s): 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Adult
  • Androgen Antagonists / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Dihydrotestosterone / metabolism*
  • Dihydrotestosterone / pharmacology
  • Endometrium / cytology*
  • Endometrium / metabolism*
  • Female
  • Flutamide / pharmacology
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Hysterectomy
  • Leiomyoma / surgery
  • Middle Aged
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • Premenopause
  • Prolactin / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Stromal Cells / metabolism*
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1
  • Uterine Neoplasms / surgery

Substances

  • Androgen Antagonists
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • SOD1 protein, human
  • Dihydrotestosterone
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Flutamide
  • Prolactin
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • superoxide dismutase 2