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


METHODS
Prospective basic research study.


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


METHODS
None.


METHODS
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Navarro
Francisco J
FJ
The Clinical Research Center, The Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, Virginia, USA.
Mirkin
Sebastian
S
Archer
David F
DF
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000235:genetics*; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008222:Lymphokines / Q000235:genetics*; D011374:Progesterone / Q000494:pharmacology*; D011446:Prospective Studies; D020033:Protein Isoforms; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D019700:Thrombospondin 1 / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D020033:Protein Isoforms; D020845:Selective Estrogen Receptor Modulators; D019700:Thrombospondin 1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020849:Raloxifene Hydrochloride; D011374:Progesterone; D004958:Estradiol