Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria.
Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria.
Toxicol Appl Pharmacol. 2021 Jan 15;411:115381. doi: 10.1016/j.taap.2020.115381. Epub 2020 Dec 24.
Polycystic ovarian syndrome (PCOS), is a multifactorial endocrine disorder in women of reproductive age. It usually associates with metabolic disorders (MDs), which aggravates the risk of infertility, cardiometabolic events and associated comorbidities in women with PCOS. Adiponectin, a circulating protein produced by adipocytes, which has been suggested to inversely correlate with MDs. Spironolactone, a non-selective mineralocorticoid receptor (MR) antagonist, has been in wide clinical use for several decades. Herein, we investigated the effects of low dose spironolactone (LDS) and the role of adiponectin in endocrine-metabolic disturbances in experimentally-induced PCOS rats. Eighteen female Wistar rats (160-180 g) were randomly allotted into 3 groups and treated with vehicle (p.o.), letrozole (LET; 1 mg/kg) and LET + LDS (0.25 mg/kg), once daily for 21 days, respectively. The results showed that LET-treated animals had features of PCOS, characterized by elevated plasma testosterone and prolactin, increased body weight gain and ovarian weight as well as disrupted ovarian cytoarchitecture and degenerated follicles. Additionally, elevated fasting blood glucose, 1 h-postload glucose and plasma insulin, impaired glucose tolerance, insulin resistance, reduced insulin sensitivity, increased plasma and ovarian lipid profile, plasma lipid peroxidation, TNF-α, IL-6 and decreased plasma glutathione peroxidase and glutathione content were observed. These alterations were associated with decreased circulating adiponectin and were reversed when treated with LDS. The present results suggest that LDS ameliorates endocrine-metabolic disturbances and inflammation-related comorbidities associated with LET-induced PCOS by modulating circulating androgen-adiponectin status.
多囊卵巢综合征（PCOS）是一种发生于育龄期妇女的多因素内分泌紊乱疾病。它通常与代谢紊乱（MDs）相关联，这会增加患有 PCOS 的女性不孕、心脏代谢事件和相关合并症的风险。脂联素是一种由脂肪细胞产生的循环蛋白，据报道它与 MDs 呈负相关。螺内酯是一种非选择性盐皮质激素受体（MR）拮抗剂，已在临床上广泛应用数十年。在此，我们研究了低剂量螺内酯（LDS）的作用以及脂联素在实验性诱导的 PCOS 大鼠内分泌代谢紊乱中的作用。18 只雌性 Wistar 大鼠（160-180g）被随机分为 3 组，分别给予 vehicle（口服）、来曲唑（LET；1mg/kg）和 LET+LDS（0.25mg/kg），每天 1 次，连续 21 天。结果显示，LET 处理的动物表现出 PCOS 的特征，表现为血浆睾酮和催乳素升高、体重增加和卵巢重量增加以及卵巢细胞结构破坏和退化卵泡。此外，还观察到空腹血糖、1h 负荷后血糖和血浆胰岛素升高、葡萄糖耐量受损、胰岛素抵抗、胰岛素敏感性降低、血浆和卵巢脂质谱升高、血浆脂质过氧化、TNF-α、IL-6 降低以及血浆谷胱甘肽过氧化物酶和谷胱甘肽含量降低。这些变化与循环脂联素减少有关，而用 LDS 治疗则可以逆转这些变化。本研究结果表明，LDS 通过调节循环雄激素-脂联素状态改善 LET 诱导的 PCOS 相关的内分泌代谢紊乱和炎症相关的合并症。
