Effects of genistein on the periovulatory expression of messenger ribonucleic acid for matrix metalloproteinases and tissue inhibitors of metalloproteinases in the rat ovary

Komar, CM; Matousek, M; Mitsube, Kenrokuro; Mikuni, M; Brännström, Mats; Te, Curry

doi:10.1530/rep.0.1210259

Cited by 15 publications

(5 citation statements)

References 6 publications

(8 reference statements)

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“…Matrix metalloproteinase-9 was elevated in fluid of preovulatory follicles of pigs [95] and horses [96] and in formative corpora lutea or luteinized granulosa cells of rats [97], cattle [98,99], and human beings [100]. Collagenase-3 (MMP-13), which degrades collagens I-III, was increased in preovulatory rat follicles [101,102]. Cathepsin L (a lysosomal cysteine protease member of the papain family) and ADAMTS-1 (a disintegrin and metalloproteinase with thrombospondin-like motifs) were induced in preovulatory follicles of rodents; mice with a mutant progesterone receptor gene, which fail to ovulate, expressed MMP-2, -9, and -13 upon gonadotropic stimulation; however, mRNAs encoding cathepsin L and ADAMTS-1 were reduced [103].…”

Section: Additional Considerationsmentioning

confidence: 99%

Proteolytic Mechanisms in the Ovulatory Folliculo-Luteal Transformation

Murdoch

Gottsch²

2003

Connective Tissue Research

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The connective tissue matrix of the wall of ovarian follicles is degraded and remodeled during ovulatory rupture and formation of the corpus luteum. Ovarian surface epithelial cells in close contact with the apical wall of preovulatory ovine follicles secrete a urokinase-type plasminogen activator in response to surge levels of gonadotropins. Urokinase activates latent collagenases and stimulates release of tumor necrosis factor alpha from thecal endothelium. Tumor necrosis factor alpha progressively induces matrix metalloproteinase gene expression, apoptosis, and inflammatory necrosis. Collagenolysis and cellular death are a prelude to stigma formation and ovarian rupture. Ovulation is blocked by intrafollicular injection of TNFalpha or MMP-2 antisera. Unruptured follicles luteinize but are deficient in collagenous/vascularized trabeculae, and produce less progesterone than their control luteal counterparts. It appears that TNFalpha, via MMP-2 induction, contributes to the reorganization of an ovulatory follicle into a fully competent corpus luteum.

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Section: Additional Considerationsmentioning

confidence: 99%

Proteolytic Mechanisms in the Ovulatory Folliculo-Luteal Transformation

Murdoch

Gottsch²

2003

Connective Tissue Research

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“…Several genes have been characterized as downstream targets of RUNX1 in various hematopoietic cells, although the transcriptional regulation of RUNX1 on these genes was found to be cell-type specific (17). Among these genes, a few have been found to be up-regulated in periovulatory ovaries, such as cyclin-dependent kinase inhibitor 1A (cdkn1a) (18,19), tissue inhibitor of metalloproteinase-1 (Timp1) (20,21), and matrix metalloproteinase 13 (Mmp13) (22,23). Studies with promoter regions of RUNX1 target genes have demonstrated the importance of the cooperation of RUNX1 with other transcription factors in regulating gene expression (19).…”

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confidence: 99%

Luteinizing Hormone-Induced RUNX1 Regulates the Expression of Genes in Granulosa Cells of Rat Periovulatory Follicles

Curry

2006

Molecular Endocrinology

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The LH surge induces specific transcription factors that regulate the expression of a myriad of genes in periovulatory follicles to bring about ovulation and luteinization. The present study determined 1) the localization of RUNX1, a nuclear transcription factor, 2) regulation of Runx1 mRNA expression, and 3) its potential function in rat ovaries. Up-regulation of mRNA and protein for RUNX1 is detected in preovulatory follicles after human chorionic gonadotropin (hCG) injection in gonadotropin-treated immature rats as well as after the LH surge in cycling animals by in situ hybridization and immunohistochemical and Western blot analyses. The regulation of Runx1 mRNA expression was investigated in vitro using granulosa cells from rat preovulatory ovaries. Treatments with hCG, forskolin, or phorbol 12 myristate 13-acetate stimulated Runx1 mRNA expression. The effects of hCG were reduced by inhibitors of protein kinase A, MAPK kinase, or p38 kinase, indicating that Runx1 expression is regulated by the LH-initiated activation of these signaling mediators. In addition, hCG-induced Runx1 mRNA expression was inhibited by a progesterone receptor antagonist and an epidermal growth factor receptor tyrosine kinase inhibitor, whereas amphiregulin stimulated Runx1 mRNA expression, demonstrating that the expression is mediated by the activation of the progesterone receptor and epidermal growth factor receptor. Finally, knockdown of Runx1 mRNA by small interfering RNA decreased progesterone secretion and reduced levels of mRNA for Cyp11a1, Hapln1, Mt1a, and Rgc32. The hormonally regulated expression of Runx1 in periovulatory follicles, its involvement in progesterone production, and regulation of preovulatory gene expression suggest important roles of RUNX1 in the periovulatory process.

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“…Protein tyrosine kinases appear to be critical in the signaling cascade initiated by BSG as treatment with genistein, a protein kinase inhibitor, ablated BSG-stimulated Mmp13 expression by cultured fibroblasts [40]. Genistein also inhibited Mmp13 expression by whole rat ovaries perfused in vitro with LH [41]; it therefore seems plausible that BSG could regulate ovarian MMP13 via a similar pathway to that described in tumor-stroma interactions. In human lung fibroblasts, BSG stimulated Mmp13 expression through the p38 signaling cascade, whereas induction of Mmp2 was mediated through the phospholipase A 2 /5-lipoxygenase catalyzed pathway in breast cancer cells [40,42].…”

Section: Discussionmentioning

confidence: 91%

Expression of Basigin, an Inducer of Matrix Metalloproteinases, in the Rat Ovary1

Smedts

Curry

2005

Biology of Reproduction

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The extensive tissue remodeling that occurs during follicular development, ovulatory rupture, and the formation and regression of the corpus luteum (CL) requires local degradation of the extracellular environment by matrix metalloproteinases (MMPs). This report characterizes the expression pattern of basigin (Bsg), a putative regulator of MMP induction, in the rat ovary. An induced superovulation model (eCG/hCG) was used in immature rats to evaluate Bsg expression profiles in ovaries collected during the follicular phase, the preovulatory period, and the luteal lifespan. Levels of Bsg mRNA were unchanged through follicular growth (0-48 h post-eCG) and increased during postovulatory luteinization (24 and 48 h post-hCG; P < 0.01). Bsg expression persisted into pseudopregnancy (4-8 days post-hCG) and after functional luteal regression (12 days post-hCG). The profile of Bsg expression during regression of the CL was examined using a model of induced luteolysis. Both functional and structural regression was associated with a decline in Bsg expression levels. Bsg mRNA and protein localized to the theca of preovulatory follicles (12 h post-hCG) and formative and functional CL (24 h-8 days post-hCG). Bsg expression profiles in the induced ovulation and CL regression models were similar to observations made in naturally cycling mature rats. In the cycling ovary, Bsg signaling localized to newly forming CL, the theca of preovulatory follicles, and appeared to be lower in CL from previous estrous cycles. A putative regulatory mechanism of Bsg expression was identified using an in vitro model; treatment of cultured granulosa cells with hCG significantly augmented Bsg mRNA expression levels. The processes of ovulation and luteogenesis may be facilitated by Bsg expression and its induction or regulation of the MMPs.

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Effects of genistein on the periovulatory expression of messenger ribonucleic acid for matrix metalloproteinases and tissue inhibitors of metalloproteinases in the rat ovary

Cited by 15 publications

References 6 publications

Proteolytic Mechanisms in the Ovulatory Folliculo-Luteal Transformation

Proteolytic Mechanisms in the Ovulatory Folliculo-Luteal Transformation

Luteinizing Hormone-Induced RUNX1 Regulates the Expression of Genes in Granulosa Cells of Rat Periovulatory Follicles

Expression of Basigin, an Inducer of Matrix Metalloproteinases, in the Rat Ovary1

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