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Hum. Reprod. Advance Access published online on April 13, 2006
Human Reproduction, doi:10.1093/humrep/del035
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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
Received November 17, 2005
Revised December 26, 2005
Accepted January 23, 2006

Article

A novel selective progesterone receptor modulator asoprisnil (J867) down-regulates the expression of EGF, IGF-I, TGF{beta}3 and their receptors in cultured uterine leiomyoma cells

Jiayin Wang 1, Noriyuki Ohara 1, Zhuo Wang 1, Wei Chen 1, Akira Morikawa 1, Hiroko Sasaki 1, Deborah A. DeManno 2, Kristof Chwalisz 2, and Takeshi Maruo 1 *

1 Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan
2 TAP Pharmaceutical Products Inc., Lake Forest, IL, USA

* To whom correspondence should be addressed.
Takeshi Maruo, E-mail: maruo{at}kobe-u.ac.jp


  Abstract

BACKGROUND: This study was conducted to evaluate the effects of a novel selective progesterone receptor modulator (SPRM) asoprisnil on the expression of growth factors and their receptors and on growth factor-induced proliferation of cultured uterine leiomyoma and matching myometrial cells. METHODS: The expression of epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I) and transforming growth factor (TGF{beta}3) was assessed by immunocyto-chemistry and semi-quantitative RT-PCR. The expression of phosphorylated EGF receptor (p-EGFR), IGF-I receptor {alpha} subunit (IGF-IR{alpha}) and phosphorylated TGF{beta} receptor type II (p-TGF{beta} RII) was assessed by Western blot analysis. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. RESULTS: Treatment with 10-7 M asoprisnil decreased EGF, IGF-I and TGF{beta}3 mRNA and protein expression as well as p-EGFR, IGF-IR{alpha} and p-TGF{beta} RII protein expression in leiomyoma cells cultured for 72 h. EGF (100 ng/ml), IGF-I (100 ng/ml) and TGF{beta}3 (10 ng/ml) increased the number of viable leiomyoma cells cultured for 72 h, whereas the concomitant treatment with 10-7 M asoprisnil antagonized the growth factor-induced increase in leiomyoma cell proliferation. In cultured myometrial cells, however, asoprisnil affected neither the growth factor and their receptor expression nor the cell proliferation. CONCLUSION: Asoprisnil inhibits the expression of EGF, IGF-I, TGF{beta}3 and their receptors in cultured leiomyoma cells without affecting their expressions in myometrial cells.

Keywords: asoprisnil/epidermal growth factor/insulin-like growth factor-I/leiomyoma/selective progesterone receptor modulator/transforming growth factor {beta}3.
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