Patel Roshni, Pathak Zarna, Deshpande Shrikalp, Shah Gaurang
Department of Pharmacology and Pharmacy Practice, K. B. Institute of Pharmaceutical Education and Research, Near Gh-6 circle, Sector-23, Gandhinagar, Gujarat, India, 382023.
National Institute of Pharmaceutical Education and Research, Ahmedabad, Gujarat, India.
Reprod Sci. 2023 Feb;30(2):622-632. doi: 10.1007/s43032-022-01039-1. Epub 2022 Aug 5.
Polycystic ovary syndrome (PCOS) represents a spectrum of disorders, associated with hyperandrogenism, oligoanovulation, and polycystic ovaries. Aldose reductase (AR), a rate-limiting enzyme of polyol pathway, is responsible for maintenance of intracellular osmotic balance, facilitation of oocyte development, and organization of the granulosa cells in the ovary. Cyclic changes in the aldose reductase level were found during the 4-5 days estrus cycle in rat, which is regulated by gonadotropin-releasing hormone (GnRH). Irregular GnRH secretion in PCOS patients may lead to altered aldose reductase expression and ovarian dysfunction. Treatment with a novel AR inhibitor, fidarestat, has been reported to improve erythrocyte sorbitol content in diabetic patients. Hence, the potential role AR in pathogenesis of PCOS was investigated by inhibiting AR with fidarestat in PCOS-induced rats. Pre-pubertal female Sprague-Dawley rats were divided into five groups. PCOS is induced either by administering letrozole or by feeding high-fat diet for 90 days. After induction of PCOS, fidarestat treatment was given for 28 days and various parameters were measured. In PCOS-induced rats, parameters like food intake, body weight, insulin, OGTT, triglycerides, cholesterol, prolonged diestrus phase, ovary weight, and immunohistological localization AR were found to be significantly altered. Fidarestat treatment significantly improved ovary weight, ovarian aldose reductase localization in PCOS-induced rats. Improvement in all these parameters suggest involvement of aldose reductase in the pathogenesis of PCOS.
多囊卵巢综合征（PCOS）代表一系列疾病，与高雄激素血症、排卵稀少和多囊卵巢有关。醛糖还原酶（AR）是多元醇途径的限速酶，负责维持细胞内渗透压平衡、促进卵母细胞发育以及卵巢颗粒细胞的组织。在大鼠4-5天的发情周期中发现醛糖还原酶水平有周期性变化，这受促性腺激素释放激素（GnRH）调节。PCOS患者GnRH分泌不规则可能导致醛糖还原酶表达改变和卵巢功能障碍。据报道，用新型AR抑制剂非达司他治疗可改善糖尿病患者的红细胞山梨醇含量。因此，通过在PCOS诱导的大鼠中用非达司他抑制AR来研究AR在PCOS发病机制中的潜在作用。青春期前雌性Sprague-Dawley大鼠分为五组。通过给予来曲唑或喂养高脂饮食90天诱导PCOS。诱导PCOS后，给予非达司他治疗28天并测量各种参数。在PCOS诱导的大鼠中，发现食物摄入量、体重、胰岛素、口服葡萄糖耐量试验、甘油三酯、胆固醇、延长的间情期、卵巢重量和AR的免疫组织学定位等参数有显著改变。非达司他治疗显著改善了PCOS诱导大鼠的卵巢重量和卵巢醛糖还原酶定位。所有这些参数的改善表明醛糖还原酶参与了PCOS的发病机制。
