| Developmental programming: differential effects of prenatal testosterone excess on insulin target tissues. | |
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MedLine Citation:
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PMID: 20843997 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Polycystic ovarian syndrome (PCOS) is the leading cause of infertility in reproductive-aged women with the majority manifesting insulin resistance. To delineate the causes of insulin resistance in women with PCOS, we determined changes in the mRNA expression of insulin receptor (IR) isoforms and members of its signaling pathway in tissues of adult control (n = 7) and prenatal testosterone (T)-treated (n = 6) sheep (100 mg/kg twice a week from d 30-90 of gestation), the reproductive/metabolic characteristics of which are similar to women with PCOS. Findings revealed that prenatal T excess reduced (P < 0.05) expression of IR-B isoform (only isoform detected), insulin receptor substrate-2 (IRS-2), protein kinase B (AKt), peroxisome proliferator-activated receptor-γ (PPARγ), hormone-sensitive lipase (HSL), and mammalian target of rapamycin (mTOR) but increased expression of rapamycin-insensitive companion of mTOR (rictor), and eukaryotic initiation factor 4E (eIF4E) in the liver. Prenatal T excess increased (P < 0.05) the IR-A to IR-B isoform ratio and expression of IRS-1, glycogen synthase kinase-3α and -β (GSK-3α and -β), and rictor while reducing ERK1 in muscle. In the adipose tissue, prenatal T excess increased the expression of IRS-2, phosphatidylinositol 3-kinase (PI3K), PPARγ, and mTOR mRNAs. These findings provide evidence that prenatal T excess modulates in a tissue-specific manner the expression levels of several genes involved in mediating insulin action. These changes are consistent with the hypothesis that prenatal T excess disrupts the insulin sensitivity of peripheral tissues, with liver and muscle being insulin resistant and adipose tissue insulin sensitive. |
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Authors:
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Shadia E Nada; Robert C Thompson; Vasantha Padmanabhan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-09-15 |
Journal Detail:
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Title: Endocrinology Volume: 151 ISSN: 1945-7170 ISO Abbreviation: Endocrinology Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-21 Completed Date: 2010-11-04 Revised Date: 2011-11-01 |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: United States |
Other Details:
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Languages: eng Pagination: 5165-73 Citation Subset: AIM; IM |
Affiliation:
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Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109-5404, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adipose Tissue
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drug effects,
metabolism* Androgens / metabolism, pharmacology Animals Female Insulin / metabolism Insulin Receptor Substrate Proteins / metabolism* Insulin Resistance / physiology Intracellular Signaling Peptides and Proteins / metabolism Liver / drug effects, metabolism* Muscle, Skeletal / drug effects, metabolism* PPAR gamma / metabolism Protein-Serine-Threonine Kinases / metabolism Proto-Oncogene Proteins c-akt / metabolism Receptor, Insulin / metabolism* Reverse Transcriptase Polymerase Chain Reaction Sheep Signal Transduction / drug effects, physiology Sterol Esterase / metabolism TOR Serine-Threonine Kinases Testosterone / metabolism*, pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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P01 HD 44234/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Androgens; 0/Insulin Receptor Substrate Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/PPAR gamma; 11061-68-0/Insulin; 58-22-0/Testosterone; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.10.1/Receptor, Insulin; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.1.1.13/Sterol Esterase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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