Transient prenatal androgen exposure produces metabolic syndrome in adult female rats.
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 ( approximately 2.5- vs. approximately 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.
Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Marek
M
Demissie
Milos
M
Lazic
Eileen M
EM
Foecking
Fraser
F
Aird
Andrea
A
Dunaif
Jon E
JE
Levine
D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004041:Dietary Fats / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D024821:Metabolic Syndrome / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013739:Testosterone / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D004041:Dietary Fats; D007328:Insulin; D014280:Triglycerides; D013739:Testosterone; D002784:Cholesterol