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

• Published in: Endocrine and metabolic science 2022-12, Vol.9-10, p.100123, Article 100123
• Main Authors: Areleogbe, Stephanie E., Peter, Mmenyene U., Oniyide, Adesola A., Akintayo, Christopher O., Fafure, Adedamola A., Oyeleke, Mosunmola B., Ajadi, Isaac O., Amusa, Oluwatobi A., Ayodeji, Aturamu, Olaniyi, Kehinde S.
• Format: Article
• Language: English
• Subjects: Hypothalamus; Inflammation; Kisspeptin; Mineralocorticoids; Ovary
• ISSN: 2666-3961; 2666-3961
• DOI: 10.1016/j.endmts.2022.100123

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. 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. 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. The present study therefore demonstrates that MR blockade by low-dose spironolactone alleviates hypothalamic-ovarian dysfunction associated with PCOS by improving hypothalamic kisspeptin level. •PCOS is characterized with hypothalamic-ovarian dysfunction (HOD).•HOD is associated with decreased hypothalamic kisspeptin.•MR blockade by low-dose spironolactone (LDS) alleviates HOD.•LDS improves hypothalamic kisspeptin level.