Regulation of matrix metalloproteinase-19 messenger RNA expression in the rat ovary.
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.
Department of Obstetrics and Gynecology, Chandler Medical Center, University of Kentucky, Lexington, Kentucky 40536-0298, USA. mjo2@uky.edu
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Thomas E
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D000818:Animals; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005260:Female; D005498:Follicular Phase; D005786:Gene Expression Regulation; D006067:Gonanes / Q000494:pharmacology; D006107:Granulosa Cells / Q000201:enzymology; D006727:Hormone Antagonists / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008183:Luteal Phase; D007986:Luteinizing Hormone / Q000494:pharmacology; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases / Q000235:genetics*; D015735:Mifepristone / Q000494:pharmacology; D010053:Ovary / Q000201:enzymology*; D010060:Ovulation; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013799:Theca Cells / Q000201:enzymology; D014018:Tissue Distribution
D016861:Cyclooxygenase Inhibitors; D006067:Gonanes; D006727:Hormone Antagonists; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D015735:Mifepristone; D007986:Luteinizing Hormone; D003513:Cycloheximide; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases; C108362:matrix metalloproteinase 19; C053238:onapristone; D007213:Indomethacin