Department of Pharmacology and Pharmacy Practice, K. B. Institute of Pharmaceutical Education and Research, Gandhinagar, India.
Department of Pharmacology, L. M. College of Pharmacy, Ahmedabad, India.
Arch Med Res. 2018 Apr;49(3):154-163. doi: 10.1016/j.arcmed.2018.08.001. Epub 2018 Aug 10.
Insulin sensitizers like metformin and pioglitazone are clinically used since last decades for the treatment of PCOS, but their efficacy and possible role in PCOS patients remains questionable. Also, the mechanism by which these insulin sensitizers show effect is not clear.
To evaluate the effect of metformin and pioglitazone on leutinizing hormone and follicle stimulating hormone receptor mRNA expression, hyperandrogenism and insulin resistance in high fat diet induced and letrozole induced PCOS in rats.
Pre-pubertal female rats were divided into four groups: group I received normal pellet diet and group II, III and IV received high fat diet. After 105 d of dietary manipulation, metformin and pioglitazone treatment was given to group III and group IV animals respectively for 21 d. Similarly, adult female rats were divided into four groups: group I received 1% carboxymethyl cellulose (CMC) and group II, III, IV received letrozole for 21 d. After 21 d of letrozole administration, metformin and pioglitazone treatment was given to group III and group IV animals respectively for 21 d. Oral glucose tolerance test, lipid profile, fasting glucose, insulin, estrus cycle, hormonal profile, ovary weight, leutinizing hormone receptor and follicle stimulating hormone receptor mRNA expression was measured. Polycystic ovarian morphology was assessed through histopathological changes of ovary.
Metformin and pioglitazone treatment improve both metabolic and reproductive parameters of PCOS including hyperinsulinemia and hyperandrogenism. LH receptor and FSH receptor mRNA expression were altered by pioglitazone and metformin treatment.
几十年来,二甲双胍和吡格列酮等胰岛素增敏剂一直被临床用于治疗 PCOS,但它们的疗效及其在 PCOS 患者中的可能作用仍存在争议。此外,这些胰岛素增敏剂发挥作用的机制尚不清楚。
评估二甲双胍和吡格列酮对高脂肪饮食诱导和来曲唑诱导的 PCOS 大鼠黄体生成素和卵泡刺激素受体 mRNA 表达、高雄激素血症和胰岛素抵抗的影响。
将青春期前雌性大鼠分为 4 组:第 1 组给予普通颗粒饮食,第 2、3 和 4 组给予高脂肪饮食。经过 105 天的饮食处理后,第 3 和第 4 组大鼠分别给予二甲双胍和吡格列酮治疗 21 天。同样,成年雌性大鼠分为 4 组:第 1 组给予 1%羧甲基纤维素(CMC),第 2、3 和 4 组给予来曲唑治疗 21 天。来曲唑给药 21 天后,第 3 和第 4 组大鼠分别给予二甲双胍和吡格列酮治疗 21 天。进行口服葡萄糖耐量试验、血脂谱、空腹血糖、胰岛素、发情周期、激素谱、卵巢重量、黄体生成素受体和卵泡刺激素受体 mRNA 表达检测。通过卵巢组织病理学变化评估多囊卵巢形态。
二甲双胍和吡格列酮治疗可改善 PCOS 的代谢和生殖参数,包括高胰岛素血症和高雄激素血症。吡格列酮和二甲双胍治疗可改变 LH 受体和 FSH 受体 mRNA 的表达。