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-alpha (TNF-alpha), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), testosterone, 17-beta 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-alpha, GGT/LDH and plasma testosterone while it decreased plasma 17-beta 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.