Estrogen and selective estrogen receptor modulators regulate vascular endothelial growth factor and soluble vascular endothelial growth factor receptor 1 in human endometrial stromal cells

Fertil Steril. 2010 May 15;93(8):2680-6. doi: 10.1016/j.fertnstert.2009.08.056. Epub 2009 Oct 13.

Abstract

Objective: To determine whether 17beta-estradiol (E(2)) and selective estrogen receptor modulators can regulate vascular endothelial growth factor (VEGF) and soluble VEGF receptor 1 (sVEGFR-1) as a VEGF antagonist in human endometrial stromal cells (ESCs).

Design: In vitro experiment.

Setting: Research laboratory at Kansai Medical University.

Patient(s): Sixteen patients undergoing hysterectomy for benign reasons.

Intervention(s): The ESCs were cultured with E(2), 4-hydroxytamoxifen (OHT), and raloxifene.

Main outcome measure(s): The VEGF and sVEGFR-1 messenger RNA (mRNA) levels in ESCs were determined using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Free (unbound) VEGF and sVEGFR-1 protein levels from ESCs were measured using ELISA kits.

Result(s): The E(2) significantly induced VEGF mRNA levels, whereas E2 caused a significant decrease in sVEGFR-1 messenger RNA (mRNA) levels. The E(2) or OHT significantly increased the VEGF production levels and attenuated the sVEGFR-1 production compared with control, but raloxifene had no significant effect. The decrease in levels of free VEGF was proportional to the increase in sVEGFR-1 levels in the culture media of ESCs.

Conclusion(s): The E(2) or OHT stimulates VEGF production and concurrently attenuates sVEGFR-1 production in ESCs. This consequential increase in VEGF:sVEGFR-1 ratio might enhance the biological effects of VEGF on the angiogenic environment in human endometrium.

MeSH terms

  • Adult
  • Endometrium / blood supply
  • Endometrium / cytology*
  • Estradiol / pharmacology*
  • Female
  • Humans
  • RNA, Messenger / metabolism
  • Raloxifene Hydrochloride / pharmacology*
  • Selective Estrogen Receptor Modulators / pharmacology*
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism*
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / pharmacology
  • Vascular Endothelial Growth Factor A / biosynthesis*
  • Vascular Endothelial Growth Factor Receptor-1 / biosynthesis*

Substances

  • RNA, Messenger
  • Selective Estrogen Receptor Modulators
  • Vascular Endothelial Growth Factor A
  • Tamoxifen
  • afimoxifene
  • Raloxifene Hydrochloride
  • Estradiol
  • Vascular Endothelial Growth Factor Receptor-1