Mannerås Louise, Cajander Stefan, Holmäng Agneta, Seleskovic Zamira, Lystig Theodore, Lönn Malin, Stener-Victorin Elisabet
Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, Göteborg University, Box 434, SE-405 30 Göteborg, Sweden.
Endocrinology. 2007 Aug;148(8):3781-91. doi: 10.1210/en.2007-0168. Epub 2007 May 10.
Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, abdominal obesity, and insulin resistance. However, its etiology is unclear, and its management is often unsatisfactory or requires a diversified approach. Here, we describe a new rat PCOS model, the first to exhibit both ovarian and metabolic characteristics of the syndrome. Female rats received the nonaromatizable androgen dihydrotestosterone (DHT) or the aromatase inhibitor letrozole by continuous administration, beginning before puberty, to activate androgen receptors. Adult DHT rats had irregular cycles, polycystic ovaries characterized by cysts formed from atretic follicles, and a diminished granulosa layer. They also displayed metabolic features, including increased body weight, increased body fat, and enlarged mesenteric adipocytes, as well as elevated leptin levels and insulin resistance. All letrozole rats were anovulatory and developed polycystic ovaries with structural changes strikingly similar to those in human PCOS. Our findings suggest that the formation of a "hyperplastic" theca interna reflects the inclusion of luteinized granulosa cells in the cyst wall rather than true hyperplasia. We conclude that the letrozole model is suitable for studies of the ovarian features of human PCOS, while the DHT model is suitable for studies of both ovarian and metabolic features of the syndrome.
多囊卵巢综合征（PCOS）是一种复杂的内分泌和代谢紊乱疾病，与排卵功能障碍、高雄激素血症、腹部肥胖和胰岛素抵抗有关。然而，其病因尚不清楚，治疗往往不尽人意或需要采用多种方法。在此，我们描述了一种新的大鼠PCOS模型，这是首个同时表现出该综合征卵巢和代谢特征的模型。雌性大鼠在青春期前开始通过持续给药接受非芳香化雄激素双氢睾酮（DHT）或芳香化酶抑制剂来曲唑，以激活雄激素受体。成年DHT大鼠有月经周期不规律、多囊卵巢（其特征为由闭锁卵泡形成的囊肿）以及颗粒层变薄。它们还表现出代谢特征，包括体重增加、体脂增加、肠系膜脂肪细胞增大，以及瘦素水平升高和胰岛素抵抗。所有来曲唑大鼠均无排卵，并发展出多囊卵巢，其结构变化与人类PCOS极为相似。我们的研究结果表明，“增生性”内膜细胞层的形成反映了囊肿壁中包含黄体化颗粒细胞而非真正的增生。我们得出结论，来曲唑模型适用于研究人类PCOS的卵巢特征，而DHT模型适用于研究该综合征的卵巢和代谢特征。
