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Progesterone receptor isoforms profile, modulate matrix metalloproteinase 2 expression in the decidua
Shlomit Goldman1, Eliezer Shalev
1Laboratory for Research in Reproductive Sciences, Department of Obstetrics and Gynecology, Ha'Emek Medical Center, Afula, Israel.
American Journal of Obstetrics and Gynecology
|August 7, 2007
Summary
Progesterone’s effect on matrix metalloproteinase-2 (MMP-2) in human decidua depends on the progesterone receptor (PR) profile. PRB activation by progesterone reduces MMP-2, while PRA and PRC show complex regulatory roles.
Area of Science:
- Reproductive biology
- Endocrinology
- Molecular biology
Background:
- Matrix metalloproteinase-2 (MMP-2) plays a critical role in decidual tissue remodeling.
- Progesterone is a key hormone in pregnancy, influencing decidual function.
- The progesterone receptor (PR) exists in various isoforms (PRA, PRB, PRC) with potentially distinct functions.
Purpose of the Study:
- To investigate the impact of progesterone on MMP-2 expression in human decidua.
- To elucidate the role of different progesterone receptor (PR) isoforms (PRA, PRB, PRC) in mediating MMP-2 regulation.
Main Methods:
- MMP secretion was assessed using zymography.
- MMP2 transcript levels were quantified via semiquantitative reverse transcriptase-polymerase chain reaction.
- Luciferase reporter assays were employed to determine progesterone's effect on the MMP2 promoter activity.
- The influence of PR isoforms (PRA, PRB, PRC) on MMP-2 expression was examined using complementary DNA transfection.
Main Results:
- Progesterone significantly decreased MMP-2 expression in decidua overexpressing the PRB isoform.
- Conversely, progesterone increased pro-MMP-2 expression in decidua with overexpressed PRA or PRC isoforms.
- While PRA did not alter MMP2 promoter activity, PRB and PRC transfection decreased it; progesterone further increased promoter activity with PRC.
Conclusions:
- Progesterone inhibits MMP-2 expression in decidua primarily through the PRB pathway.
- The PR isoforms exhibit complex interactions: PRA represses PRB, and PRC appears to repress both PRA and PRB.
- These findings highlight the isoform-specific regulatory mechanisms of progesterone on MMP-2 in the human decidua.
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