Document Detail

Effects of levonorgestrel-releasing IUS and progesterone receptor modulator PRM CDB-2914 on uterine leiomyomas.
MedLine Citation:
PMID:  17531625     Owner:  NLM     Status:  MEDLINE    
We have found that the use of levonorgestrel-releasing IUS results in a remarkable decrease in endometrial proliferation and a remarkable increase in apoptosis in the endometrium; therefore, it is effective for long-term management of menorrhagic women with uterine myomas because of the striking reduction in menorrhagia. This prompted us to characterize the effects of progesterone (P(4)) and progesterone receptor modulator (PRM) CDB2914 on uterine myoma growth. In vitro studies with cultured uterine leiomyoma cells and normal myometrial cells revealed that P(4) stimulated the proliferative activity in leiomyoma cells, but not in normal myometrial cells. P(4) increased EGF expression, whereas E(2) augmented EGF-R expression in leiomyoma cells, indicating that P(4) and E(2) act in combination to stimulate leiomyoma cell growth. P(4) also increased Bcl-2 expression and decreased TNF-alpha expression in those cells. Unlike the EGF expression, IGF-I expression in leiomyoma cells was inhibited by P(4). These results suggest that P(4) has dual actions on leiomyoma growth: one is to stimulate the growth through up-regulating EGF and Bcl-2 expression, and the other is to inhibit the growth through down-regulating IGF-I expression in the cells. By contrast, CDB2914 inhibited proliferation and stimulated apoptosis of leiomyoma cells without affecting normal myometrial cells. Furthermore, CDB2914 inhibited vascular endothelial growth factor and adrenomedullin expression in leiomyoma cells, but not in normal myometrial cells. The cell type-specific action of CDB2914 on leiomyoma cells, without affecting the surrounding normal myometrial cells, is meaningful for understanding the usefulness of CDB2914 in the medical treatment of uterine myomas.
Takeshi Maruo; Noriyuki Ohara; Hiroya Matsuo; Qin Xu; Wei Chen; Regine Sitruk-Ware; Elof D B Johansson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2007-03-21
Journal Detail:
Title:  Contraception     Volume:  75     ISSN:  0010-7824     ISO Abbreviation:  Contraception     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-05-28     Completed Date:  2007-10-02     Revised Date:  2010-02-04    
Medline Journal Info:
Nlm Unique ID:  0234361     Medline TA:  Contraception     Country:  United States    
Other Details:
Languages:  eng     Pagination:  S99-103     Citation Subset:  IM    
Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan.
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MeSH Terms
Contraceptive Agents, Female / pharmacology
Endometrium / blood supply,  drug effects,  metabolism
Intrauterine Devices, Medicated*
Leiomyoma / drug therapy*,  metabolism
Levonorgestrel / pharmacology
Norpregnadienes / pharmacology*
Progesterone / metabolism
Receptors, Progesterone / drug effects
Uterine Neoplasms / drug therapy*,  metabolism
Reg. No./Substance:
0/Contraceptive Agents, Female; 0/Norpregnadienes; 0/Receptors, Progesterone; 0/ulipristal; 57-83-0/Progesterone; 797-63-7/Levonorgestrel

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