| Androgen receptor antagonism and an insulin sensitizer block the advancement of vaginal opening by high-fat diet in mice. | |
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MedLine Citation:
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PMID: 19605781 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Reduced hypothalamic sensitivity to steroid negative feedback may contribute to the onset of puberty. In high fat-fed rodents, the timing of vaginal opening (VO) is advanced, suggesting that puberty begins earlier. Because obesity can increase androgens, which interfere with normal steroid feedback in adult females, we hypothesized that androgens reduce hypothalamic sensitivity to negative feedback during puberty and that blocking androgen action would prevent advanced VO in high fat-fed mice. Age at VO was examined in mice fed high-fat or low-fat diets from weaning and treated with the androgen receptor antagonist flutamide or vehicle (controls). VO was advanced in high-fat vs. low-fat controls, and flutamide blocked this advancement. VO was also delayed in low fat-fed flutamide-treated females, suggesting involvement of androgens in the timing of normal puberty. We next investigated if high-fat diet-induced insulin resistance contributes to early VO, as elevated insulin can stimulate androgen production. VO was examined in mice on either diet treated with the insulin sensitizer metformin. Metformin blocked high-fat advancement of VO but did not alter the timing of VO in low fat-fed mice. Insulin was elevated in high fat-fed females that had undergone VO compared with age-matched low fat-fed or metformin-treated animals on either diet that had not undergone VO. Together, these data suggest a model in which metabolic changes induced by high-fat diet, including transient increased circulating insulin, act in part by increasing androgen action to influence the timing of puberty in females. |
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Authors:
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Diana S Brill; Suzanne M Moenter |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-07-15 |
Journal Detail:
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Title: Biology of reproduction Volume: 81 ISSN: 1529-7268 ISO Abbreviation: Biol. Reprod. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-11-25 Completed Date: 2010-01-05 Revised Date: 2011-03-03 |
Medline Journal Info:
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Nlm Unique ID: 0207224 Medline TA: Biol Reprod Country: United States |
Other Details:
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Languages: eng Pagination: 1093-8 Citation Subset: IM |
Affiliation:
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Department of Medicine, University of Virginia, Charlottesville, Virginia, USA. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Androgen Antagonists / pharmacology Animals Body Weight / drug effects, physiology Diet, Fat-Restricted Dietary Fats / metabolism* Fatty Acids, Nonesterified / blood Female Flutamide / pharmacology Hypoglycemic Agents / pharmacology Insulin / metabolism* Insulin Resistance Metformin / pharmacology Mice Mice, Inbred C57BL Receptors, Androgen / metabolism* Sexual Maturation / drug effects*, physiology* Testosterone / blood |
| Grant Support | |
ID/Acronym/Agency:
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U54 HD028934-16A16852/HD/NICHD NIH HHS; U54 HGG62293//PHS HHS |
| Chemical | |
Reg. No./Substance:
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0/Androgen Antagonists; 0/Dietary Fats; 0/Fatty Acids, Nonesterified; 0/Hypoglycemic Agents; 0/Receptors, Androgen; 11061-68-0/Insulin; 13311-84-7/Flutamide; 58-22-0/Testosterone; 657-24-9/Metformin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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