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This Article Full Text Full Text (PDF) All Versions of this Article: 295/2/E262    most recent 90208.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Demissie, M. Articles by Levine, J. E. PubMed PubMed Citation Articles by Demissie, M. Articles by Levine, J. E.

TRANSLATIONAL PHYSIOLOGY

Transient prenatal androgen exposure produces metabolic syndrome in adult female rats

¹Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University, Chicago; ²Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinios; and ³Department of Endocrinology, Diabetology, and Isotope Therapy, Wroclaw Medical School, Wroclaw, Poland

Submitted 2 February 2008 ; accepted in final form 5 June 2008

Androgen exposure during intrauterine life in nonhuman primates and in sheep results in a phenocopy of the reproductive and metabolic features of polycystic ovary syndrome (PCOS). Such exposure also results in reproductive features of PCOS in rodents. We investigated whether transient prenatal androgen treatment produced metabolic abnormalities in adult female rats and the mechanisms of these changes. Pregnant dams received free testosterone or vehicle injections during late gestation, and their female offspring were fed regular or high-fat diet (HFD). At 60 days of age, prenatally androgenized (PA) rats exhibited significantly increased body weight; parametrial and subcutaneous fat; serum insulin, cholesterol and triglyceride levels; and hepatic triglyceride content (all P < 0.0125). There were no significant differences in insulin sensitivity by intraperitoneal insulin tolerance test or insulin signaling in liver or skeletal muscle. HFD had similar effects to PA on body weight and composition as well as on circulating triglyceride levels. HFD further increased hepatic triglyceride content to a similar extent in both PA and control rats. In PA rats, HFD did not further increase circulating insulin, triglyceride, or cholesterol levels. In control rats, HFD increased insulin levels, but to a lesser extent than PA alone (2.5- vs. 12-fold, respectively). We conclude that transient prenatal androgen exposure produces features of the metabolic syndrome in adult female rats. Dyslipidemia and hepatic steatosis appear to be mediated by PA-induced increases in adiposity, whereas hyperinsulinemia appears to be a direct result of PA.

prenatal androgen exposure; metabolic syndrome; polycystic ovary syndrome; hepatic steatosis