| Developmental programming: insulin sensitizer treatment improves reproductive function in prenatal testosterone-treated female sheep. | |
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MedLine Citation:
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PMID: 20555028 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Prenatal testosterone (T) excess causes reproductive and metabolic disruptions including insulin resistance, attributes of women with polycystic ovary syndrome. This study tested the hypothesis that insulin resistance contributes toward severity of reproductive disruptions in prenatally T-treated females. Pregnant sheep were injected im with 100 mg of T-propionate semiweekly from d 30-90 of gestation. Immediately after the first breeding season, a subset of controls and prenatal T-treated (TR) sheep were administered an insulin sensitizer (rosiglitazone; 8 mg/d) orally for 8 months. Untreated control and prenatal T-treated females (T group) were studied in parallel. Biochemical analyses revealed rosiglitazone to be safe for use in sheep. Glucose tolerance tests performed before and after the insulin sensitizer treatment found that insulin sensitizer decreased cumulative insulin, cumulative insulin/glucose ratio, and insulin area under the curve by about 50% and increased the insulin sensitivity index by about 70% in the TR compared with the T group. Twenty percent of TR females showed a reduced number of cycles in the second relative to first breeding season as opposed to 80% of T group females showing such deterioration. Insulin sensitizer treatment also decreased the number of aberrant cycles (>/=18 d) during the second breeding season in the TR group relative to the first as opposed to the T group females showing an increase in the second breeding season relative to the first. These findings provide evidence that insulin sensitizer treatment prevents further deterioration of the reproductive axis in prenatal T-treated sheep, a finding of translational relevance to women with polycystic ovary syndrome. |
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Authors:
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Almudena Veiga-Lopez; James S Lee; Vasantha Padmanabhan |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. Date: 2010-06-16 |
Journal Detail:
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Title: Endocrinology Volume: 151 ISSN: 1945-7170 ISO Abbreviation: Endocrinology Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-27 Completed Date: 2010-09-08 Revised Date: 2011-08-03 |
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: 4007-17 Citation Subset: AIM; IM |
Affiliation:
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Department of Pediatrics and Reproductive Sciences Program, University of Michigan, Ann Arbor, Michigan 48109-0404, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Drug Evaluation, Preclinical Estrous Cycle / blood, drug effects, metabolism Female Fetal Development / drug effects* Hypoglycemic Agents / pharmacology Insulin / metabolism*, pharmacology Insulin Resistance / physiology Liver / metabolism, physiopathology Polycystic Ovary Syndrome / chemically induced, drug therapy, metabolism, pathology Pregnancy Prenatal Exposure Delayed Effects / chemically induced*, drug therapy*, metabolism, physiopathology Reproduction / drug effects*, physiology Sheep Testosterone / adverse effects*, pharmacology Thiazolidinediones / pharmacology, therapeutic use* |
| Grant Support | |
ID/Acronym/Agency:
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P01 HD44232/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Hypoglycemic Agents; 0/Thiazolidinediones; 11061-68-0/Insulin; 122320-73-4/rosiglitazone; 58-22-0/Testosterone |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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