| Metformin: direct inhibition of rat ovarian theca-interstitial cell proliferation. | |
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MedLine Citation:
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PMID: 22608319 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To determine whether metformin has direct effects on ovarian theca-interstitial (T-I) cell proliferation through activation of adenosine monophosphate-activated protein kinase (AMPK). DESIGN: In vitro experimental study. SETTING: Academic medical center laboratory. ANIMAL(S): Immature Sprague-Dawley female rats. INTERVENTION(S): Ovarian T-I cells were isolated, purified, and cultured in the absence (control) or presence of insulin (1 μg/mL) with or without metformin or other activators/inhibitors of AMPK (AICAR, compound C). MAIN OUTCOME MEASURE(S): Proliferation assessed by determination of expression levels of proteins involved in cell cycle progression, cyclin D3, and cyclin-dependent kinase 4 (CDK4) with Western blot analysis, and determination of DNA synthesis with bromodeoxyuridine (BrdU) incorporation assay; activation of AMPK, Erk1/2, and S6K1 determined by Western blot analysis with the use of antibodies specific for the phosphorylated (activated) forms. RESULT(S): Metformin inhibited insulin-induced ovarian T-I cell proliferation and the up-regulation of the cell cycle regulatory proteins, cyclin D3 and CDK4. Metformin independently activated AMPK in a dose-dependent manner. Treatment with metformin inhibited insulin-induced activation of Erk1/2 and S6K1. This effect was reversed with the addition of compound C, a known AMPK inhibitor. CONCLUSION(S): Metformin directly inhibits proliferation of ovarian T-I cells via an AMPK-dependent mechanism. These findings further validate the potential benefits of metformin in the treatment of conditions associated with hyperinsulinemia and excessive growth of ovarian T-I cells (such as polycystic ovary syndrome). |
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Authors:
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Matthew A Will; Murugesan Palaniappan; Helle Peegel; Pradeep Kayampilly; K M J Menon |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-05-17 |
Journal Detail:
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Title: Fertility and sterility Volume: 98 ISSN: 1556-5653 ISO Abbreviation: Fertil. Steril. Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-07-03 Completed Date: 2012-09-05 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0372772 Medline TA: Fertil Steril Country: United States |
Other Details:
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Languages: eng Pagination: 207-14 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, Michigan, USA. matwill@med.umich.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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AMP-Activated Protein Kinases
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metabolism Animals Cell Cycle Checkpoints / drug effects, physiology Cell Proliferation / drug effects* Cells, Cultured Drug Evaluation, Preclinical Enzyme Activation / drug effects Female Hypoglycemic Agents / pharmacology MAP Kinase Signaling System / drug effects Metformin / pharmacology* Ovary / cytology, drug effects* Rats Rats, Sprague-Dawley Ribosomal Protein S6 Kinases / metabolism Theca Cells / cytology, drug effects*, physiology |
| Grant Support | |
ID/Acronym/Agency:
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HD 38424/HD/NICHD NIH HHS; R01 HD038424/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Hypoglycemic Agents; 657-24-9/Metformin; EC 2.7.11.1/AMP-Activated Protein Kinases; EC 2.7.11.1/Ribosomal Protein S6 Kinases; EC 2.7.11.1/S6K1 protein, rat |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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