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


METHODS
In vitro experiment.


METHODS
Research laboratory at Kansai Medical University.


METHODS
Sixteen patients undergoing hysterectomy for benign reasons.


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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Okada
Hidetaka
H
Department of Obstetrics and Gynecology, Kansai Medical University, Osaka, Japan. hokada@hirakata.kmu.ac.jp
Tsutsumi
Akihiro
A
Imai
Miyuki
M
Nakajima
Tatsuya
T
Yasuda
Katsuhiko
K
Kanzaki
Hideharu
H
D000328:Adult; D004717:Endometrium / Q000098:blood supply / Q000166:cytology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism*; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis*
D012333:RNA, Messenger; D020845:Selective Estrogen Receptor Modulators; D042461:Vascular Endothelial Growth Factor A; D013629:Tamoxifen; C016601:afimoxifene; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D040281:Vascular Endothelial Growth Factor Receptor-1