| Gonadotropin-Releasing Hormone-I or -II Interacts with IGF-I/Akt But Not Connexin 43 in Human Granulosa Cell Apoptosis. | |
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MedLine Citation:
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PMID: 22112812 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Background:We have recently demonstrated that GnRH-I or -II can induce apoptosis in immortalized human granulosa cells by activating the caspase signaling cascade. Whether GnRH-I or -II can affect other regulators such as Bcl-2 family members, IGF-I, or gap junctions and the mechanisms involved are unknown.Methods:Immortalized human granulosa cells were treated with GnRH-I, GnRH-II, IGF-I, or antide (a GnRH-I receptor antagonist), in various combinations. Cell proliferation and apoptotic changes were evaluated by cell counting, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and immunoblotting. Activated or total protein expression of IGF-I receptor, Akt, connexin 43 (Cx43), or caspase-3 with and without dominant-negative Akt (an Akt-suppressing vector), wortmannin (a phosphatidylinositol-3-kinase inhibitor), or Cx43 small interfering RNA transfection were assessed by immunoblotting. Gap junctional communication was determined by dye transfer assay.Results:GnRH-I or -II inhibited cell proliferation, induced TUNEL-positive cells, and increased caspase-3 activities but had no effects on Bcl-2 family members. IGF-I increased cell proliferation, decreased TUNEL-positive cells and caspase-3 activities, and increased Akt activities, and these effects were attenuated by GnRH-I or -II. Effects of IGF-I on caspase-3 activities were attenuated by dominant-negative Akt or wortmannin. GnRH-I or -II decreased dye transfer, increased Cx43 phosphorylation, and increased caspases-3 activities even after Cx43 knockdown.Conclusion:GnRH-I or -II induces apoptosis in human granulosa cells through a caspase-3-dependent extrinsic pathway rather than a Bcl-2 family-dependent intrinsic pathway and attenuates the antiapoptotic action of IGF-I through Akt. Cx43-induced gap junctional changes do not initiate granulosa cell apoptosis but likely result from apoptosis induced by GnRH-I or -II. |
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Authors:
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In-Sun Hong; C Klausen; Anthony P Cheung; Peter C K Leung |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-23 |
Journal Detail:
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Title: The Journal of clinical endocrinology and metabolism Volume: - ISSN: 1945-7197 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-24 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375362 Medline TA: J Clin Endocrinol Metab Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V6H 3V5. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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