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Regulation of matrix metalloproteinase-19 messenger RNA expression in the rat ovary
1Department of Obstetrics and Gynecology, Chandler Medical Center, University of Kentucky, Lexington, Kentucky 40536-0298, USA. mjo2@uky.edu
Abstract:
Matrix metalloproteinases (MMPs) are instrumental in the constant tissue remodeling in the ovary. An induction of MMP-19 mRNA in periovulatory follicles has been reported in mouse ovaries. However, little is known about MMP-19 expression during the follicular and luteal periods or about the ovarian regulation of MMP-19 mRNA expression. We examined the expression pattern of MMP-19 mRNA during various reproductive phases and the periovulatory regulation of MMP-19 mRNA in the rat ovary. In gonadotropin-primed, immature rat ovaries, levels of MMP-19 mRNA transiently increased during both follicular growth and ovulation. The MMP-19 mRNA was localized to the theca-interstitial layer of growing follicles and to the granulosa and theca-interstitial layers of periovulatory follicles. A similar expression pattern of MMP-19 mRNA in periovulatory follicles was observed in ovaries from naturally cycling adult rats. Accumulation of MMP-19 mRNA was detected in regressing corpus luteum. The regulation of MMP-19 mRNA expression during the periovulatory period was investigated via in vivo studies and through in vitro culture studies on follicular cells. The hCG-induction of MMP-19 mRNA was mimicked by treating granulosa cells, but not theca-interstitial cells, from preovulatory follicles with LH or activators of the protein kinase (PK) A or PKC pathways. Cycloheximide blocked the LH- or forskolin-induced MMP-19 mRNA expression, demonstrating the requirement for new protein synthesis. In contrast, blocking activation of the progesterone receptor or prostaglandin synthesis had no effect on the increase in MMP-19 mRNA expression. In conclusion, the induction of MMP-19 mRNA suggests an important role of this proteinase during follicular growth, ovulation, and luteal regression.
Insights
Matrix metalloproteinase-19 (MMP-19) mRNA expression increases during ovarian follicular growth, ovulation, and luteal regression. Its induction is regulated by luteinizing hormone (LH) and protein kinase pathways, requiring new protein synthesis.
Area of Science:
- Reproductive biology
- Molecular endocrinology
- Ovarian physiology
Background:
- Matrix metalloproteinases (MMPs) are crucial for ovarian tissue remodeling.
- MMP-19 mRNA induction is noted in periovulatory follicles in mice.
- Limited information exists on MMP-19 expression across the ovarian cycle and its regulation.
Purpose of the Study:
- To investigate MMP-19 mRNA expression patterns throughout the rat ovarian cycle.
- To elucidate the periovulatory regulation of MMP-19 mRNA expression in the rat ovary.
Main Methods:
- Analysis of MMP-19 mRNA expression in rat ovaries during follicular and luteal phases.
- Localization studies of MMP-19 mRNA in ovarian follicles.
- In vivo and in vitro studies using gonadotropin stimulation and follicular cell cultures to investigate regulatory pathways.
- Treatment with LH, protein kinase activators, cycloheximide, progesterone receptor antagonists, and prostaglandin synthesis inhibitors.
Main Results:
- MMP-19 mRNA levels increased during follicular growth and ovulation in immature rat ovaries.
- MMP-19 mRNA was localized to theca-interstitial and granulosa cells of developing and periovulatory follicles.
- Similar expression patterns were observed in naturally cycling adult rats, with accumulation in regressing corpora lutea.
- LH, PKA, and PKC pathways, but not progesterone or prostaglandin signaling, mediated hCG-induced MMP-19 mRNA expression in granulosa cells.
- LH- or forskolin-induced MMP-19 mRNA expression required de novo protein synthesis.
Conclusions:
- MMP-19 mRNA is dynamically expressed during key ovarian events including follicular growth, ovulation, and luteal regression.
- The periovulatory induction of MMP-19 mRNA is regulated by LH and protein kinase pathways, dependent on new protein synthesis.
- These findings suggest a significant role for MMP-19 in ovarian remodeling processes.
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