Document Detail


Rescue of obesity-induced infertility in female mice due to a pituitary-specific knockout of the insulin receptor.
MedLine Citation:
PMID:  20816095     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Obesity is associated with insulin resistance in metabolic tissues such as adipose, liver, and muscle, but it is unclear whether nonclassical target tissues, such as those of the reproductive axis, are also insulin resistant. To determine if the reproductive axis maintains insulin sensitivity in obesity in vivo, murine models of diet-induced obesity (DIO) with and without intact insulin signaling in pituitary gonadotrophs were created. Diet-induced obese wild-type female mice (WT DIO) were infertile and experienced a robust increase in luteinizing hormone (LH) after gonadotropin-releasing hormone (GnRH) or insulin stimulation. By contrast, both lean and obese mice with a pituitary-specific knockout of the insulin receptor (PitIRKO) exhibited reproductive competency, indicating that insulin signaling in the pituitary is required for the reproductive impairment seen in DIO and that the gonadotroph maintains insulin sensitivity in a setting of peripheral insulin resistance.
Authors:
Kathryn J Brothers; Sheng Wu; Sara A DiVall; Marcus R Messmer; C Ronald Kahn; Ryan S Miller; Sally Radovick; Fredric E Wondisford; Andrew Wolfe
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Cell metabolism     Volume:  12     ISSN:  1932-7420     ISO Abbreviation:  Cell Metab.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-06     Completed Date:  2010-11-04     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  101233170     Medline TA:  Cell Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  295-305     Citation Subset:  IM    
Copyright Information:
2010 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Diet
Estrous Cycle / physiology
Female
Gonadotropin-Releasing Hormone / metabolism
Infertility, Female / etiology*,  genetics
Insulin / metabolism
Insulin Resistance / physiology
Luteinizing Hormone / metabolism
Male
Mice
Mice, Knockout
Obesity / complications*
Pituitary Gland / metabolism,  physiology*
Receptor, Insulin / genetics*,  metabolism
Reproduction / physiology
Signal Transduction / physiology
Grant Support
ID/Acronym/Agency:
K08 DK078644/DK/NIDDK NIH HHS; P60 DK079637-04/DK/NIDDK NIH HHS; R01 DK33201/DK/NIDDK NIH HHS; R01 HD034551/HD/NICHD NIH HHS; R01 HD034551-10/HD/NICHD NIH HHS; R01 HD044608-06/HD/NICHD NIH HHS; R01HD044608/HD/NICHD NIH HHS; U54 HD041859/HD/NICHD NIH HHS; U54 HD041859-01A19001/HD/NICHD NIH HHS; U54 HD041859-06/HD/NICHD NIH HHS; U54 HD58820/HD/NICHD NIH HHS; U54-HD28934/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Insulin; 33515-09-2/Gonadotropin-Releasing Hormone; 9002-67-9/Luteinizing Hormone; EC 2.7.10.1/Receptor, Insulin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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