PMID- 19366846
OWN - NLM
STAT- MEDLINE
DCOM- 20090806
LR  - 20220317
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 94
IP  - 7
DP  - 2009 Jul
TI  - Simvastatin protects against the development of endometriosis in a nude mouse 
      model.
PG  - 2489-94
LID - 10.1210/jc.2008-2802 [doi]
AB  - CONTEXT: Endometriosis is a common condition associated with infertility and 
      pelvic pain in women. Recent in vitro studies have shown that statins decrease 
      proliferation of endometrial stroma (ES) and inhibit angiogenesis. OBJECTIVE: The 
      aim was to evaluate effects of simvastatin on development of endometriosis in a 
      nude mouse model. METHODS: Proliferative phase human endometrial biopsies were 
      obtained from healthy donors and established as organ cultures or used to isolate 
      ES cells. To establish endometriosis in the nude mouse, endometrial tissues were 
      maintained in 1 nm estradiol (E) for 24 h and subsequently injected into 
      ovariectomized nude mice. Mice (n = 37) were treated with E (8 mg, SILASTIC 
      capsule implants; made in author laboratory) alone or with E plus simvastatin (5 
      or 25 mg/kg x d) for 10 d beginning 1 d after tissue injection (from three 
      donors). Mice were killed and examined for disease. Effects of simvastatin on 
      matrix metalloproteinase-3 (MMP-3) were evaluated in cultures of ES cells. 
      PRIMARY OUTCOME: The number and size of endometriotic implants were measured. 
      RESULTS: Simvastatin induced a dose-dependent decrease of the number and size of 
      endometrial implants in mice. At the highest dose of simvastatin, the number of 
      endometrial implants decreased by 87%, and the volume by 98%. Simvastatin also 
      induced a concentration-dependent decrease in MMP-3 in the absence and presence 
      of inflammatory challenge (using IL-1alpha). CONCLUSIONS: Simvastatin exerted a 
      potent inhibitory effect on the development of endometriosis in the nude mouse. 
      Mechanisms of action of simvastatin may include inhibition of MMP-3. The present 
      findings may lead to the development of novel treatments of endometriosis 
      involving statins.
FAU - Bruner-Tran, Kaylon L
AU  - Bruner-Tran KL
AD  - Women's Reproductive Health Research Center, Department of Obstetrics and 
      Gynecology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, 
      USA.
FAU - Osteen, Kevin G
AU  - Osteen KG
FAU - Duleba, Antoni J
AU  - Duleba AJ
LA  - eng
GR  - R01 HD055648/HD/NICHD NIH HHS/United States
GR  - U54 HD052668/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090414
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Anticholesteremic Agents)
RN  - 4TI98Z838E (Estradiol)
RN  - AGG2FN16EV (Simvastatin)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Animals
MH  - Anticholesteremic Agents/pharmacology/therapeutic use
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Drug Evaluation, Preclinical
MH  - Endometriosis/pathology/*prevention & control
MH  - Estradiol/administration & dosage
MH  - Female
MH  - Humans
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Mice
MH  - Mice, Nude
MH  - Middle Aged
MH  - Simvastatin/administration & dosage/pharmacology/*therapeutic use
MH  - Time Factors
MH  - Transplantation, Heterologous
MH  - Uterine Diseases/pathology/*prevention & control
MH  - Young Adult
PMC - PMC2708947
EDAT- 2009/04/16 09:00
MHDA- 2009/08/07 09:00
PMCR- 2010/07/01
CRDT- 2009/04/16 09:00
PHST- 2009/04/16 09:00 [entrez]
PHST- 2009/04/16 09:00 [pubmed]
PHST- 2009/08/07 09:00 [medline]
PHST- 2010/07/01 00:00 [pmc-release]
AID - jc.2008-2802 [pii]
AID - 6572 [pii]
AID - 10.1210/jc.2008-2802 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2009 Jul;94(7):2489-94. doi: 10.1210/jc.2008-2802. Epub 
      2009 Apr 14.