Progesterone receptor modulator CDB-2914 down-regulates vascular endothelial growth factor, adrenomedullin and their receptors and modulates progesterone receptor content in cultured human uterine leiomyoma cells.
BACKGROUND
This study was conducted to evaluate the effects of graded concentrations (10(-8), 10(-7) and 10(-6) M) of progesterone receptor (PR) modulator CDB-2914 on the protein contents of PR, of vascular endothelial growth factor (VEGF), adrenomedullin (ADM) and their receptors in cultured human uterine leiomyoma and matching myometrial cells.


METHODS
PR-A, PR-B, VEGF-A, VEGF-B, VEGF receptor (VEGFR)-1, VEGFR-2, ADM and ADM receptor (ADMR) contents were assessed by Western blot analysis.


RESULTS
Treatment with 100 ng/ml progesterone increased VEGF-A, VEGF-B and ADM contents in cultured leiomyoma cells and normal myometrial cells. The concomitant treatment with 10(-6) M CDB-2914 significantly decreased the progesterone-induced VEGF-A, VEGF-B and ADM contents in cultured leiomyoma cells but not in normal myometrial cells. CDB-2914 treatment alone decreased VEGFR-1, VEGFR-2 and ADMR contents in cultured leiomyoma cells but not in normal myometrial cells. CDB-2914 treatment increased PR-A and decreased PR-B contents in cultured leiomyoma cells in a dose-dependent manner compared with untreated cultures, whereas no significant changes in PR isoform contents were observed in normal myometrial cells.


CONCLUSIONS
These results suggest that CDB-2914 down-regulates VEGF, ADM and their receptor contents and modulates PR isoform contents in cultured leiomyoma cells in a cell-type-specific manner.
Xu
Qin
Q
Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan.
Ohara
Noriyuki
N
Chen
Wei
W
Liu
Jin
J
Sasaki
Hiroko
H
Morikawa
Akira
A
Sitruk-Ware
Regine
R
Johansson
Elof D B
ED
Maruo
Takeshi
T
D053607:Adrenomedullin / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000378:metabolism*; D009215:Myometrium / Q000378:metabolism; D009649:Norpregnadienes / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000096:biosynthesis* / Q000378:metabolism*; D014594:Uterine Neoplasms / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000378:metabolism
D009649:Norpregnadienes; D011980:Receptors, Progesterone; D042461:Vascular Endothelial Growth Factor A; C097314:progesterone receptor B; D053607:Adrenomedullin; C094854:ulipristal