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Hum. Reprod. Advance Access originally published online on May 23, 2006
Human Reproduction 2006 21(9):2408-2416; doi:10.1093/humrep/del159
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Qin Xu1, Noriyuki Ohara1, Wei Chen1, Jin Liu1, Hiroko Sasaki1, Akira Morikawa1, Regine Sitruk-Ware2, Elof D.B. Johansson2 and Takeshi Maruo1,3

1 Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan and 2 Center for Biomedical Research, The Population Council, New York, NY, USA

3 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-Cho, Chuo-Ku, Kobe 650-0017, Japan. E-mail: maruo{at}kobe-u.ac.jp

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.

Key words: adrenomedullin/CDB-2914/leiomyoma/progesterone receptor modulator/vascular endothelial growth factor


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