PMID- 18281245
OWN - NLM
STAT- MEDLINE
DCOM- 20080527
LR  - 20171116
IS  - 1460-2350 (Electronic)
IS  - 0268-1161 (Linking)
VI  - 23
IP  - 4
DP  - 2008 Apr
TI  - Selective progesterone receptor modulator asoprisnil down-regulates collagen 
      synthesis in cultured human uterine leiomyoma cells through up-regulating 
      extracellular matrix metalloproteinase inducer.
PG  - 944-51
LID - 10.1093/humrep/den025 [doi]
AB  - BACKGROUND: A recent clinical trial demonstrated that selective progesterone 
      receptor modulator asoprisnil is effective in reducing uterine leiomyoma volume. 
      We investigated the effects of asoprisnil in vitro on the expression of the 
      extracellular matrix (ECM)-remodeling enzymes and collagens in cultured leiomyoma 
      and matching normal myometrial cells. METHODS: The expression of extracellular 
      matrix metalloproteinase inducer (EMMPRIN), matrix metalloproteinases (MMPs), 
      tissue inhibitors of MMP (TIMPs) and collagens were assessed by western blot 
      analysis. RESULTS: Untreated cultured leiomyoma cells had significantly lower 
      EMMPRIN (P < 0.05), MMP-1 (P < 0.05) and membrane type 1-MMP (MT1-MMP) (P < 0.01) 
      protein contents, but significantly higher TIMP-1 (P < 0.05), TIMP-2 (P < 0.01), 
      type I (P < 0.05) and type III (P < 0.01) collagen protein contents compared with 
      untreated cultured myometrial cells. Treatment with asoprisnil at concentrations 
      > or =10(-7) M for 48 h significantly (P < 0.05) increased EMMPRIN, MMP-1 and 
      MT1-MMP protein contents, and decreased TIMP-1 (P < 0.05), TIMP-2 (P < 0.01), 
      type I (P < 0.01) and type III (P < 0.05 at 10(-7) M; P < 0.01 at 10(-6) M) 
      collagen protein contents in cultured leiomyoma cells compared with control 
      cultures. However, asoprisnil treatment did not affect the protein contents of 
      ECM-remodeling enzymes and collagens in cultured myometrial cells. CONCLUSIONS: 
      These results suggest that asoprisnil may reduce collagen deposit in the ECM of 
      cultured leiomyoma cells through decreasing collagen synthesis and enhancing the 
      expression of EMMPRIN, MMPs and TIMPs without comparable effects on cultured 
      myometrial cells.
FAU - Morikawa, Akira
AU  - Morikawa A
AD  - Department of Obstetrics and Gynecology, Kobe University Graduate School of 
      Medicine, Kobe, Japan.
FAU - Ohara, Noriyuki
AU  - Ohara N
FAU - Xu, Qin
AU  - Xu Q
FAU - Nakabayashi, Koji
AU  - Nakabayashi K
FAU - DeManno, Deborah A
AU  - DeManno DA
FAU - Chwalisz, Kristof
AU  - Chwalisz K
FAU - Yoshida, Shigeki
AU  - Yoshida S
FAU - Maruo, Takeshi
AU  - Maruo T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080215
PL  - England
TA  - Hum Reprod
JT  - Human reproduction (Oxford, England)
JID - 8701199
RN  - 0 (Estrenes)
RN  - 0 (Oximes)
RN  - 0 (Receptors, Progesterone)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 136894-56-9 (Basigin)
RN  - 72W09924WP (asoprisnil)
RN  - 9007-34-5 (Collagen)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Adult
MH  - Basigin/*metabolism
MH  - Cells, Cultured
MH  - Collagen/*biosynthesis/drug effects
MH  - Down-Regulation
MH  - Estrenes/*pharmacology
MH  - Female
MH  - Gene Expression Regulation, Enzymologic
MH  - Humans
MH  - In Vitro Techniques
MH  - Leiomyoma/drug therapy/metabolism
MH  - Matrix Metalloproteinases/metabolism
MH  - Middle Aged
MH  - Myometrium/drug effects
MH  - Oximes/*pharmacology
MH  - Receptors, Progesterone/*drug effects
MH  - Tissue Inhibitor of Metalloproteinases/metabolism
MH  - Up-Regulation
MH  - Uterine Neoplasms/drug therapy/metabolism
EDAT- 2008/02/19 09:00
MHDA- 2008/05/28 09:00
CRDT- 2008/02/19 09:00
PHST- 2008/02/19 09:00 [pubmed]
PHST- 2008/05/28 09:00 [medline]
PHST- 2008/02/19 09:00 [entrez]
AID - den025 [pii]
AID - 10.1093/humrep/den025 [doi]
PST - ppublish
SO  - Hum Reprod. 2008 Apr;23(4):944-51. doi: 10.1093/humrep/den025. Epub 2008 Feb 15.