Demissie Marek, Lazic Milos, Foecking Eileen M, Aird Fraser, Dunaif Andrea, Levine Jon E
Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Am J Physiol Endocrinol Metab. 2008 Aug;295(2):E262-8. doi: 10.1152/ajpendo.90208.2008. Epub 2008 Jun 10.
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.
在非人灵长类动物和绵羊的子宫内生活期间暴露于雄激素会导致多囊卵巢综合征（PCOS）生殖和代谢特征的拟表型。这种暴露也会导致啮齿动物出现PCOS的生殖特征。我们研究了短暂的产前雄激素治疗是否会在成年雌性大鼠中产生代谢异常以及这些变化的机制。怀孕的母鼠在妊娠后期接受游离睾酮或载体注射，其雌性后代喂食常规或高脂饮食（HFD）。在60日龄时，产前雄激素化（PA）的大鼠体重显著增加；子宫旁和皮下脂肪增加；血清胰岛素、胆固醇和甘油三酯水平升高；肝脏甘油三酯含量增加（所有P<0.0125）。通过腹腔内胰岛素耐量试验或肝脏或骨骼肌中的胰岛素信号传导，胰岛素敏感性没有显著差异。HFD对体重、组成以及循环甘油三酯水平的影响与PA相似。HFD在PA大鼠和对照大鼠中进一步将肝脏甘油三酯含量增加到相似程度。在PA大鼠中，HFD没有进一步增加循环胰岛素、甘油三酯或胆固醇水平。在对照大鼠中，HFD增加了胰岛素水平，但程度低于单独使用PA（分别约为2.5倍和12倍）。我们得出结论，短暂的产前雄激素暴露会在成年雌性大鼠中产生代谢综合征的特征。血脂异常和肝脂肪变性似乎是由PA诱导的肥胖增加介导的，而高胰岛素血症似乎是PA的直接结果。
