Effect of raloxifene, 17beta-estradiol, and progesterone on mRNA for vascular endothelial growth factor isoforms 121 and 165 and thrombospondin-1 in Ishikawa cells

Fertil Steril. 2003 Jun;79(6):1409-15. doi: 10.1016/s0015-0282(03)00350-9.

Abstract

Objective: To compare the mRNA expression of vascular endothelial growth factor (VEGF) 121 and 165 isoforms and thrombospondin-1 (TSP-1) after raloxifene, 17beta-E(2), and P administration in cultured Ishikawa cells.

Design: Prospective basic research study.

Setting: Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, Virginia.

Patient(s): None.

Intervention(s): Ishikawa cells were cultured in vitro. Raloxifene, 17beta-E(2), and P at concentrations of 0.01, 0.1, and 1.0 microM were added to confluent cells.

Main outcome measures: The VEGF 121 and 165 isoforms and TSP-1 mRNA expression from treated Ishikawa cells were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR).

Result(s): 17beta-Estradiol increased both VEGF 121 and 165 mRNA compared to control. Raloxifene did not increase either VEGF 121 or 165 mRNA above control values. Progesterone at all concentrations did not increase VEGF 121 isoform mRNA, whereas VEGF 165 isoform was minimally increased by P at the lowest concentration. Progesterone and raloxifene increased TSP-1 mRNA expression. 17beta-Estradiol did not stimulate TSP-1 mRNA expression at any concentration.

Conclusion(s): Raloxifene did not stimulate VEGF 121 and 165, whereas it increased TSP-1 mRNA synthesis in Ishikawa cells. Our hypothesis is that raloxifene's lack of endometrial stimulation may be partly mediated by an antiangiogenic effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Cell Line
  • Dose-Response Relationship, Drug
  • Endothelial Growth Factors / genetics*
  • Estradiol / pharmacology*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Lymphokines / genetics*
  • Progesterone / pharmacology*
  • Prospective Studies
  • Protein Isoforms
  • Raloxifene Hydrochloride / pharmacology*
  • Selective Estrogen Receptor Modulators / pharmacology*
  • Thrombospondin 1 / genetics*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Angiogenesis Inhibitors
  • Endothelial Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • Protein Isoforms
  • Selective Estrogen Receptor Modulators
  • Thrombospondin 1
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Raloxifene Hydrochloride
  • Progesterone
  • Estradiol