Shah K N, Patel S S
Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, India.
Exp Clin Endocrinol Diabetes. 2014 May;122(5):261-7. doi: 10.1055/s-0034-1372578. Epub 2014 Apr 7.
Polycystic ovary syndrome is characterized by hyperandrogenemia, hyperinsulinemia and/or abnormal ovulation, which are the 3 main consequences of polycystic ovary syndrome. The occurrence of polycystic ovary syndrome is higher and 1 out of 45 women gets affected by this disorder. The pathophysiology of polycystic ovary syndrome is very unique, and many hormonal and metabolic changes occur at molecular level. Polycystic ovary syndrome is a hormonal disorder that affects multiple organ systems within the body, which is caused by insensitivity to the hormone insulin. The target organs of insulin action are skeletal muscles, adipose tissue, fibroblasts where metabolic actions of insulin take place. In polycystic ovary syndrome condition, due to insulin resistance, the actions like glucose uptake and glycogen synthesis gets declined along with exhibiting steroidogenic effect in ovaries. The action of phophatidylinositide-3 kinase varies in different tissues. It plays major role in several kinases. The inhibition and activation of phophatidylinositide-3 kinase in different tissues results in differential outcomes. The inhibition of phophatidylinositide-3 kinase in ovary leads to decreased androgen synthesis and the activation affects the positive actions of insulin like glucose uptake. Targeting the hyperandrogenemia of polycystic ovary syndrome, we can get more ameliorating action in polycystic ovary syndrome because glucose uptake, which is mediated by phophatidylinositide-3 kinase activation, is not much altered during polycystic ovary syndrome as much as the androgen levels in polycystic ovary syndrome. Therefore, it is beneficial to control the androgen level. Thus, phophatidylinositide-3 kinase inhibition can be a promising target in the treatment of polycystic ovary syndrome.
多囊卵巢综合征的特征是高雄激素血症、高胰岛素血症和/或排卵异常，这是多囊卵巢综合征的3个主要后果。多囊卵巢综合征的发病率较高，每45名女性中就有1人受此疾病影响。多囊卵巢综合征的病理生理学非常独特，在分子水平上会发生许多激素和代谢变化。多囊卵巢综合征是一种影响体内多个器官系统的激素紊乱疾病，由对胰岛素激素不敏感引起。胰岛素作用的靶器官是骨骼肌、脂肪组织、成纤维细胞，胰岛素在这些组织中发挥代谢作用。在多囊卵巢综合征情况下，由于胰岛素抵抗，葡萄糖摄取和糖原合成等作用会下降，同时卵巢会表现出类固醇生成作用。磷脂酰肌醇-3激酶在不同组织中的作用各不相同。它在几种激酶中起主要作用。在不同组织中抑制和激活磷脂酰肌醇-3激酶会产生不同的结果。抑制卵巢中的磷脂酰肌醇-3激酶会导致雄激素合成减少，而激活则会影响胰岛素的积极作用，如葡萄糖摄取。针对多囊卵巢综合征的高雄激素血症，我们可以在多囊卵巢综合征中获得更多改善作用，因为由磷脂酰肌醇-3激酶激活介导的葡萄糖摄取在多囊卵巢综合征期间的变化不像多囊卵巢综合征中的雄激素水平那么大。因此，控制雄激素水平是有益的。因此，抑制磷脂酰肌醇-3激酶可能是治疗多囊卵巢综合征的一个有前景的靶点。
