Efosa G Uhunmwangho, Adesola A Oniyide, Stephanie E Areloegbe, Olaniyi A Soetan, Christopher O Akintayo, Ayodeji Aturamu, Kehinde S Olaniyi
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The control group was given vehicle (distilled water), SPL-treated group received 0.25 mg/kg, LET-treated group received 1 mg/kg of LET and LET + SPL-treated group received a combination of LET and SPL. The administrations were done by oral gavage for 21 days uninterruptedly. Biochemical parameters such as lipid profile, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), γ-glutamyl transferase (GGT), lactate dehydrogenase (LDH), testosterone, 17-β estradiol and glutathione peroxidase (GPx) were determined with appropriate assay methods.</p><p><strong>Results: </strong>Letrozole-treated group had a significant increase in ovarian weight, plasma and ovarian triglycerides, MDA/TNF-α, GGT/LDH and plasma testosterone while it decreased plasma 17-β estradiol and plasma/ovarian high-density lipoproteins and GPx when compared with control group. In addition, histomorphological changes were observed in LET-treated group compared with control group. Nevertheless, administration of low dose SPL attenuated these perturbations.</p><p><strong>Conclusion: </strong>The present study therefore demonstrates that inhibition of mineralocorticoid receptor by low dose SPL ameliorates hyperandrogenic metabolic dysfunction in a rat model of PCOS. Therefore, low dose SPL is hereby suggested as a promising therapeutic agent in the management of PCOS.</p>","PeriodicalId":15635,"journal":{"name":"Journal of Diabetes and Metabolic Disorders","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9672164/pdf/40200_2022_Article_1097.pdf","citationCount":"0","resultStr":"{\"title\":\"Mineralocorticoid receptor blockade attenuates hyperandrogenic metabolic dysregulation in letrozole-induced PCOS rat model.\",\"authors\":\"Efosa G Uhunmwangho, Adesola A Oniyide, Stephanie E Areloegbe, Olaniyi A Soetan, Christopher O Akintayo, Ayodeji Aturamu, Kehinde S Olaniyi\",\"doi\":\"10.1007/s40200-022-01097-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Polycystic ovarian syndrome (PCOS) is a metabolic syndrome associated with mineralocorticoid receptor (MR) activation, which causes infertility in women of reproductive age. 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引用次数: 0
摘要
目的:多囊卵巢综合征(PCOS)是一种与矿皮质激素受体(MR)激活相关的代谢综合征，可导致育龄妇女不孕。螺内酯(SPL)是一种磁共振阻滞剂，对多囊卵巢综合征的治疗效果尚无定论。因此，本研究假设低剂量SPL可以改善PCOS相关的代谢功能障碍。方法:将雌性Wistar大鼠(8周龄)分为3组，分别为对照组、SPL组、来曲唑(LET)组和LET + SPL组。对照组给予载药(蒸馏水)，皂素处理组给予0.25 mg/kg, LET处理组给予1 mg/kg的LET, LET +皂素处理组给予LET和SPL联合治疗。灌胃给药21 d，不间断给药。采用相应的检测方法测定血脂、丙二醛(MDA)、肿瘤坏死因子-α (TNF-α)、γ-谷氨酰转移酶(GGT)、乳酸脱氢酶(LDH)、睾酮、17-β雌二醇、谷胱甘肽过氧化物酶(GPx)等生化指标。结果:来曲唑治疗组卵巢重量、血浆及卵巢甘油三酯、MDA/TNF-α、GGT/LDH、血浆睾酮均显著高于对照组，血浆17-β雌二醇、血浆/卵巢高密度脂蛋白、GPx均显著低于对照组。此外，与对照组相比，let处理组观察到组织形态学的变化。然而，施用低剂量的SPL减弱了这些扰动。结论:本研究表明，低剂量SPL抑制矿皮质激素受体可改善PCOS大鼠模型的高雄激素代谢功能障碍。因此，低剂量SPL被认为是治疗PCOS的一种有前景的药物。
Mineralocorticoid receptor blockade attenuates hyperandrogenic metabolic dysregulation in letrozole-induced PCOS rat model.
Purpose: Polycystic ovarian syndrome (PCOS) is a metabolic syndrome associated with mineralocorticoid receptor (MR) activation, which causes infertility in women of reproductive age. Spironolactone (SPL) is a MR blocker with inconclusive effect in the treatment of PCOS. Therefore, the present study hypothesized that low dose SPL would ameliorate metabolic dysfunction associated with PCOS.
Methods: Female Wistar rats (8-week-old) were divided into 3 groups namely: Control, SPL, Letrozole (LET)-treated and LET + SPL-treated groups. The control group was given vehicle (distilled water), SPL-treated group received 0.25 mg/kg, LET-treated group received 1 mg/kg of LET and LET + SPL-treated group received a combination of LET and SPL. The administrations were done by oral gavage for 21 days uninterruptedly. Biochemical parameters such as lipid profile, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), γ-glutamyl transferase (GGT), lactate dehydrogenase (LDH), testosterone, 17-β estradiol and glutathione peroxidase (GPx) were determined with appropriate assay methods.
Results: Letrozole-treated group had a significant increase in ovarian weight, plasma and ovarian triglycerides, MDA/TNF-α, GGT/LDH and plasma testosterone while it decreased plasma 17-β estradiol and plasma/ovarian high-density lipoproteins and GPx when compared with control group. In addition, histomorphological changes were observed in LET-treated group compared with control group. Nevertheless, administration of low dose SPL attenuated these perturbations.
Conclusion: The present study therefore demonstrates that inhibition of mineralocorticoid receptor by low dose SPL ameliorates hyperandrogenic metabolic dysfunction in a rat model of PCOS. Therefore, low dose SPL is hereby suggested as a promising therapeutic agent in the management of PCOS.
期刊介绍：
Journal of Diabetes & Metabolic Disorders is a peer reviewed journal which publishes original clinical and translational articles and reviews in the field of endocrinology and provides a forum of debate of the highest quality on these issues. Topics of interest include, but are not limited to, diabetes, lipid disorders, metabolic disorders, osteoporosis, interdisciplinary practices in endocrinology, cardiovascular and metabolic risk, aging research, obesity, traditional medicine, pychosomatic research, behavioral medicine, ethics and evidence-based practices.As of Jan 2018 the journal is published by Springer as a hybrid journal with no article processing charges. All articles published before 2018 are available free of charge on springerlink.Unofficial 2017 2-year Impact Factor: 1.816.
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