Blockade of mineralocorticoid receptor by low-dose spironolactone rescues hypothalamic-ovarian dysfunction in PCOS experimental rat model

Abstract

Background of study: Studies have shown that women with polycystic ovarian syndrome (PCOS) undergo perturbations of the hypothalamic-pituitary ovarian axis, and frequently suffer from menstrual dysfunction leading to anovulation and infertility. Involvement of mineralocorticoid receptor (MR) activation has been implicated in metabolic/endocrine disorders. Therefore, we hypothesize that mineralocorticoid receptor blocker, spironolactone (SPL) would attenuate hypothalamic-ovarian dysfunction associated with PCOS in rat model. Materials and methods: Female Wistar rats that were eight-week-old were allotted into groups. The control group received vehicle (distilled water; p.o.), letrozole (LET)-treated group received LET (1 mg/kg; p.o.), LET+SPL-treated group received letrozole plus SPL (0.25 mg/kg, p.o.). The treatment was done once daily for 21 days uninterruptedly. Results: The LET-induced PCOS animals showed increase in testosterone and LH/FSH ratio and hypothalamic and ovarian lipid profile, lipid peroxidation and inflammatory biomarkers (NF-κB and TNF-α) with a significant decrease in hypothalamic/ovarian glutathione and hypothalamic kisspeptin. However, these alterations were improved following administration of SPL. Conclusion: The present study therefore demonstrates that MR blockade by low-dose spironolactone alleviates hypothalamic-ovarian dysfunction associated with PCOS by improving hypothalamic kisspeptin level.

Keywords

• Hypothalamus
• Inflammation
• Kisspeptin
• Mineralocorticoids
• Ovary