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Home / Equine Research Bank / Mol Endocrinol / Synaptosomal-associated protein 25 gene expression is hormon...
Molecular endocrinology (Baltimore, Md.)2007; 21(10); 2487-2502; doi: 10.1210/me.2007-0042

Synaptosomal-associated protein 25 gene expression is hormonally regulated during ovulation and is involved in cytokine/chemokine exocytosis from granulosa cells.

Abstract: During ovulation, granulosa cells and cumulus cells synthesize and secrete a wide variety of factors including members of the IL cytokine family via the process of exocytosis. Exocytosis is controlled by the soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor complex consisting of proteins residing in the vesicle membrane and the plasma membrane. One of the soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor proteins, synaptosomal-associated protein (SNAP)25, is expressed abundantly in neuronal cells and is also induced transiently in the rat ovary in response to LH. Therefore, we sought to determine the molecular mechanisms controlling ovarian expression of the Snap25 gene, and the role of SNAP25 in exocytosis of secreted factors, such as ILs from cumulus cells and granulosa cells. In preovulatory follicles of equine (e) chorionic gonadotropin (CG)-primed mice, expression of Snap25 mRNA was negligible but was induced markedly 8 h after human (h) CG stimulation. In Pgr null mice Snap25 mRNA and protein levels were significantly lower at 8 h after hCG compared with wild-type mice. To analyze the molecular mechanisms by which progesterone receptor regulates this gene, a 1517-bp murine Snap25 promoter-luciferase reporter construct was generated and transfected into granulosa cell cultures. Three specificity protein (SP)-1/SP-3 sites, but not consensus activator protein 1 or cAMP response element sites, were essential for basal and forskolin/phorbol 12-myristate 13-acetate-induced promoter activity in granulosa cells. The induction was significantly suppressed by PGR antagonist, RU486. Treatment of cumulus oocyte complexes or granulosa cells with FSH/amphiregulin, LH, or forskolin/phorbol 12-myristate 13-acetate-induced elevated expression of Snap25 mRNA and increased the secretion of eight cytokine and chemokine factors. Transfection of granulosa cells with Snap25 small interfering RNA significantly reduced the levels of both SNAP25 protein and the secretion of cytokines. From these results, we conclude that progesterone-progesterone receptor-mediated SNAP25 expression in cumulus oocyte complexes and granulosa cells regulates cytokine and chemokine secretion via an exocytosis system.
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Publication Date: 2007-06-26 PubMed ID: 17595323DOI: 10.1210/me.2007-0042Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research focuses on the role of the Synaptosomal-associated protein 25 (SNAP25) gene in the process of ovulation, particularly how it influences the secretion of cytokines and chemokines from granulosa and cumulus cells. The study discovers that the expression of this gene is hormonally controlled and plays a crucial role in the exocytosis of secreted factors necessary during ovulation.

Objective and Method

  • The research primarily aimed to understand the molecular roles controlling the expression of the Snap25 gene in the ovary and its function in the exocytosis of cytokines from cumulus and granulosa cells.
  • In exploring this, they studied how the expression of Snap25 mRNA changes in preovulatory follicles in mice.
  • They developed a murine Snap25 promoter-luciferase reporter construct and transfected it into granulosa cell cultures to better grasp the molecular mechanism by which progesterone receptor regulates this gene.

Findings

  • They found that the expression of Snap25 mRNA was low in preovulatory follicles but increased significantly after human CG stimulation.
  • They discovered that in Pgr null mice, both Snap25 mRNA and protein levels were significantly lower after hCG compared to the wild-type mice, highlighting the hormones role in inducing this gene.
  • During their study of the molecular mechanism, it was discovered that three specific SP-1/SP-3 sites, but not consensus activator protein 1 or cAMP response element sites, were vital for basic and forskolin/phorbol 12-myristate 13-acetate-induced promoter activity in granulosa cells.

Hormonal Influence and Conclusion

  • The research also revealed that specific hormones/compounds like FSH/amphiregulin, LH, or forskolin/phorbol 12-myristate 13-acetate-induced elevated expression of Snap25 mRNA and increased the secretion of eight cytokine and chemokine factors.
  • Notably, by transfecting granulosa cells with Snap25 small interfering RNA, they could significantly reduce SNAP25 protein levels and the secretion of cytokines.
  • From these findings, it was concluded that progesterone-progesterone receptor-mediated Snap25 expression in cumulus oocyte complexes and granulosa cells effectively regulates cytokine and chemokine secretion via an exocytosis system.

Cite This Article

APA
Shimada M, Yanai Y, Okazaki T, Yamashita Y, Sriraman V, Wilson MC, Richards JS. (2007). Synaptosomal-associated protein 25 gene expression is hormonally regulated during ovulation and is involved in cytokine/chemokine exocytosis from granulosa cells. Mol Endocrinol, 21(10), 2487-2502. https://doi.org/10.1210/me.2007-0042

Publication

Molecular endocrinology (Baltimore, Md.)
ISSN: 0888-8809
NlmUniqueID: 8801431
Country: United States
Language: English
Volume: 21
Issue: 10
Pages: 2487-2502

Researcher Affiliations

Shimada, Masayuki
  • Department of Applied Animal Science, Graduate School of Biosphere Science, Hiroshima University, 1-4-4, Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8528, Japan. mashimad@hiroshima-u.ac.jp
Yanai, Yoshiari
    Okazaki, Tetsuji
      Yamashita, Yasuhisa
        Sriraman, Venkataraman
          Wilson, Michael C
            Richards, JoAnne S

              MeSH Terms

              • Animals
              • Chemokines / metabolism
              • Chorionic Gonadotropin / pharmacology
              • Exocytosis / genetics
              • Female
              • Gene Expression Regulation
              • Granulosa Cells / drug effects
              • Granulosa Cells / metabolism
              • Mice
              • Mice, Mutant Strains
              • Ovulation / drug effects
              • Ovulation / genetics
              • Promoter Regions, Genetic / drug effects
              • Promoter Regions, Genetic / genetics
              • RNA, Messenger / metabolism
              • RNA, Small Interfering / pharmacology
              • Receptors, Progesterone / genetics
              • Receptors, Progesterone / metabolism
              • Synaptosomal-Associated Protein 25 / antagonists & inhibitors
              • Synaptosomal-Associated Protein 25 / genetics

              Grant Funding

              • HD052023 / NICHD NIH HHS
              • HD-16229 / NICHD NIH HHS
              • HD-07495 / NICHD NIH HHS
              • MH-48989 / NIMH NIH HHS
              • R01 MH048989 / NIMH NIH HHS

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