Xu, Qin, Noriyuki Ohara, Wei Chen, Jin Liu, Hiroko Sasaki, Akira Morikawa,
Régine Sitruk-Ware,
Elof D.B. Johansson, and Takeshi Maruo. 2006.
“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,”
Human Reproduction
21(9): 2408–2416.
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.
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