绝经后多囊卵巢综合征新模型中慢性高雄激素血症的心脏代谢效应
Cardiometabolic Effects of Chronic Hyperandrogenemia in a New Model of Postmenopausal Polycystic Ovary Syndrome.
作者信息
Dalmasso Carolina, Maranon Rodrigo, Patil Chetan, Bui Elizabeth, Moulana Mohadetheh, Zhang Howei, Smith Andrew, Yanes Cardozo Licy L, Reckelhoff Jane F
机构信息
Departments of Physiology and Biophysics (C.D., R.M., C.P., L.L.Y.C., J.F.R.), Medicine (E.B., R.M., L.L.Y.C.), Psychiatry (M.M.), Radiology (H.Z., A.S.), Endocrinology (L.L.Y.C.), and Women's Health Research Center (C.D., R.M., C.P., L.L.Y.C., J.F.R.), University of Mississippi Medical Center, Jackson, Mississippi 39216.
出版信息
Endocrinology. 2016 Jul;157(7):2920-7. doi: 10.1210/en.2015-1617. Epub 2016 May 4.
Postmenopausal women who have had polycystic ovary syndrome (PCOS) and chronic hyperandrogenemia may be at a greater risk for cardiovascular disease than normoandrogenemic postmenopausal women. The cardiometabolic effect of chronic hyperandrogenemia in women with PCOS after menopause is unclear. The present study was performed to test the hypothesis that chronic hyperandrogenemia in aging female rats would have more deleterious effects on metabolic function, blood pressure, and renal function than in normoandrogenemic age-matched females. Female Sprague Dawley were implanted continuously, beginning at 4-5 weeks, with dihydrotestosterone (postmenopausal hyperandrogenemic female [PMHAF]) or placebo pellets (controls), and were studied at 13 months of age. Plasma DHT was 3-fold higher, and estradiol was 90% lower in PMHAF than controls. Body weights were higher; EchoMRI showed greater fat and lean mass; and computed tomography showed more sc and visceral adiposity in PMHAF, but with similar femur length compared with controls. Insulin resistance was present in PMHAF with higher plasma insulin, normal fasting blood glucose, abnormal oral glucose tolerance test, and higher nonfasting blood glucose. Blood pressure (radiotelemetry) was significantly higher and heart rate was lower, and renal function (glomerular filtration rate) was reduced by 40% in PMHAF. Thus the aging chronically hyperandrogenemic female rat is a new model of postmenopausal PCOS, which exhibits insulin resistance and visceral obesity, hypertension, and impairment in renal function. This new model provides a unique tool to study the deleterious effects of chronic androgen excess in postmenopausal females rats.
患有多囊卵巢综合征(PCOS)和慢性高雄激素血症的绝经后女性,可能比雄激素水平正常的绝经后女性患心血管疾病的风险更高。绝经后PCOS女性慢性高雄激素血症的心脏代谢效应尚不清楚。本研究旨在验证以下假设:与年龄匹配的雄激素水平正常的雌性大鼠相比,衰老雌性大鼠的慢性高雄激素血症对代谢功能、血压和肾功能的有害影响更大。从4至5周龄开始,对雌性斯普拉格-道利大鼠持续植入二氢睾酮(绝经后高雄激素血症雌性大鼠[PMHAF])或安慰剂丸(对照组),并在13月龄时进行研究。PMHAF组的血浆双氢睾酮(DHT)高出3倍,雌二醇低90%。PMHAF组体重更高;EchoMRI显示脂肪和瘦体重更多;计算机断层扫描显示皮下和内脏脂肪更多,但与对照组相比股骨长度相似。PMHAF组存在胰岛素抵抗,血浆胰岛素水平更高,空腹血糖正常,口服葡萄糖耐量试验异常,非空腹血糖更高。PMHAF组的血压(通过无线电遥测)显著升高,心率降低,肾功能(肾小球滤过率)降低40%。因此,衰老的慢性高雄激素血症雌性大鼠是绝经后PCOS的一种新模型,表现出胰岛素抵抗、内脏肥胖、高血压和肾功能损害。这个新模型为研究绝经后雌性大鼠慢性雄激素过量的有害影响提供了一个独特的工具。