The regulatory effects of clomiphene and tamoxifen on mTOR and LC3-II expressions in relation to autophagy in experimental polycystic ovary syndrome (PCOS)

• Published in: Molecular biology reports Vol. 49; no. 3; pp. 1721 - 1729
• Main Authors: Kuşçu, Gökçe Ceren, Gürel, Çevik, Buhur, Aylin, Oltulu, Fatih, Akman, Levent, Köse, Timur, Yavaşoğlu, Nefise Ülkü Karabay, Yavaşoğlu, Altuğ
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.03.2022; Springer Nature B.V
• Subjects: Animal Anatomy; Animal Biochemistry; Animals; Autophagy; Biomedical and Life Sciences; Citric acid; Clomiphene; Clomiphene - pharmacology; Female; Fertility Agents, Female - pharmacology; Histology; Humans; Infertility; Infertility, Female - etiology; Life Sciences; Metabolic disorders; Microtubule-Associated Proteins; Morphology; mRNA; Original Article; Ovaries; Ovulation; Ovulation Induction - methods; Polycystic ovary syndrome; Polycystic Ovary Syndrome - chemically induced; Polycystic Ovary Syndrome - drug therapy; Polycystic Ovary Syndrome - genetics; Rats; Tamoxifen; Tamoxifen - pharmacology; Tamoxifen citrate; TOR protein; TOR Serine-Threonine Kinases - genetics; mTOR; LC3-II; PCOS; Clomiphene; Tamoxifen; Autophagy
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-021-06981-y

Background Polycystic ovary syndrome (PCOS) is a metabolic disease that causes infertility due to anovulation in women in reproductive age. It is known that clomiphene citrate (CC) and tamoxifen citrate (TMX) induce ovulation in women with PCOS. In this study, we aimed to investigate the effects of CC and TMX on the autophagy pathway in PCOS. Methods and results Experimental PCOS model was induced by letrozole (1 mg/kg) in rats by gavage for 21 days. After the last letrozole administration, rats were treated TMX (1 mg/kg) or CC (1 mg/kg) for 5 days. At the end of the experimental procedures, rats in all groups were sacrificed and ovarian tissues were removed. It was observed that mRNA and protein expressions of LC3-II were significantly higher in TMX and CC groups than control and PCOS groups (p < 0.05), while mRNA and protein expressions of mTOR in TMX and CC groups were found significantly lower than control and PCOS groups (p < 0.05). Conclusions In conclusion, present study suggests that TMX and CC induce autophagy in ovaries with PCOS. Autophagy is a promising target for understanding pathophysiology of this disease and for developing more effective and safe new protocols for the treatment of PCOS-related anovulation.