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2009
2009
BACKGROUND
Although the MMP-2 promoter lacks a canonical progesterone response element (PRE), the hormone inhibits MMP-2 expression and is part of treatment protocols in gynecological invasive pathologies, including endometriosis and endometrial hyperplasia. This study aimed to explore the mechanism by which progesterone inhibits MMP-2 expression.
METHODS
The effect of progesterone on MMP-2 expression in the JAR human choriocarcinoma cell line was analyzed by gelatin zymography. MMP-2 transcript expression was studied using Northern blot and semi-quantitative RT-PCR. Rat promoter deletion analysis, electrophoretic mobility shift and chromatin immuno-precipitation assays were performed in order to locate the DNA binding site and the transcription factors involved in MMP-2 regulation.
RESULTS
Progesterone significantly decreased secretion of pro-MMP-2 and MMP-2 transcript expression level in a dose-dependent manner. Progesterone (1 microM) significantly decreased both human and rat MMP-2 promoter activity (80.1% +/- 0.3 and 81.3% +/- 0.23, respectively). Progesterone acts through the SP1 family transcription factors-binding site, located between -1433 and -1342 bp region from the transcriptional start site of the rat MMP-2 promoter, which are present in the orthologous human MMP-2 promoter. Progesterone receptor (PR), SP2, SP3 and SP4 proteins are constitutively bound to this consensus sequence.
CONCLUSION
Progesterone reduces PR and SP4 binding to the MMP-2 promoter, thereby suppressing transcription. Progesterone also promotes SP4 degradation. These novel mechanisms of MMP-2 regulation by progesterone provide the biological rationale for the use of progesterone in clinical settings associated with increased MMP-2 expression.
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2009
2009
2009
2009
2009
OBJECTIVE
To determine the optimal dose, safety, and efficacy of an estrogen receptor beta selective Chinese herbal extract, menopausal formula 101 (MF101), for treating hot flushes.
METHODS
A randomized, blinded trial in 217 postmenopausal women with hot flushes randomized to 5 or 10 g/day of MF101 or placebo for 12 weeks.
RESULTS
The effects of 5 g/day of MF101 did not differ from those of placebo. After 12 weeks, the mean percent decrease in frequency of hot flushes in the 10 g/day group was 12.9% greater than that in the placebo group (P = 0.15), the median percent decrease was 11.7% greater than that in the placebo group (P = 0.05), and the proportion of women with at least a 50% reduction in hot flushes was 16.2% greater than that in the placebo group (P = 0.03).
CONCLUSIONS
Treatment with 10 g/day of MF101 reduces the frequency of hot flushes. Trials with higher doses are planned.
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