Postnatal developmental consequences of altered insulin sensitivity in female sheep treated prenatally with testosterone

• Published in: American journal of physiology: endocrinology and metabolism 2005-11, Vol.289 (5), p.E801-E806
• Main Authors: Recabarren, Sergio E, Padmanabhan, Vasantha, Codner, Ethel, Lobos, Alejandro, Duran, Claudio, Vidal, Monica, Foster, Douglas L, Sir-Petermann, Teresa
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Body Weight; Disease Models, Animal; Female; Glucose - metabolism; Glucose Tolerance Test; Insulin - blood; Insulin - metabolism; Insulin Resistance; Male; Pregnancy; Prenatal Exposure Delayed Effects; Random Allocation; Sheep - growth & development; Sheep - metabolism; Sheep - physiology; Testosterone - pharmacology
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00107.2005

1 Laboratory of Animal Physiology and Endocrinology, Faculty of Veterinary Medicine, University of Concepción, Chillán; 4 Laboratory of Endocrinology and Metabolism, 3 Faculty of Medicine, Institute of Maternal and Child Research, University of Chile, Santiago, Chile; and 2 Reproductive Sciences Program, University of Michigan, Ann Arbor, Michigan Submitted 10 March 2005 ; accepted in final form 8 June 2005 Prenatally testosterone (T)-treated female sheep exhibit ovarian and endocrinological features that resemble those of women with polycystic ovarian syndrome (PCOS), which include luteinizing hormone excess, polyfollicular ovaries, functional hyperandrogenism, and anovulation. In this study, we determined the developmental impact of prenatal T treatment on insulin sensitivity indexes (ISI), a variable that is affected in a majority of PCOS women. Pregnant ewes were treated with 60 mg testosterone propionate intramuscularly in cottonseed oil two times a week or vehicle [control (C)] from days 30 to 90 of gestation. T-females weighed less than C-females or males ( P < 0.05) at birth and at 5 wk of age. T-females had an increased anogenital ratio. An intravenous glucose tolerance test followed by an insulin tolerance test conducted after an overnight fast at 5, 20, and 30 wk of age ( n = 7–8/group) revealed that ISI were higher at 5 than 30 wk of age in C-females, reflective of a developing insulin resistance associated with puberty. T-females had higher basal insulin levels, higher fasting insulin-to-glucose ratio, and higher incremental area under the insulin curve to the glucose challenge. The ISI of T-females was similar to that of males. No differences in ISI were evident between groups at 20 and 30 wk of age. Mean basal plasma glucose concentrations and glucose disappearance and uptake did not differ between groups at any age. Our findings suggest that prenatal T treatment leads to offspring with reduced birth weight and impaired insulin sensitivity in early postnatal life. prenatal programming; insulin sensitivity index; glucose metabolism; small for gestational age; polycystic ovary syndrome Address for reprint requests and other correspondence: S. E. Recabarren, Laboratory of Animal Physiology and Endocrinology, Faculty of Veterinary Medicine, Univ. of Concepción, Chillán, Chile (e-mail: srecabar{at}udec.cl )