1. Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction.
- Author
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Liu Y, Jiang JJ, Du SY, Mu LS, Fan JJ, Hu JC, Ye Y, Ding M, Zhou WY, Yu QH, Xia YF, Xu HY, Shi YJ, Qian SW, Tang Y, Li W, Dang YJ, Dong X, Li XY, Xu CJ, and Tang QQ
- Subjects
- Animals, Female, Humans, Mice, Rats, Androgens metabolism, Disease Models, Animal, Hyperandrogenism drug therapy, Hyperandrogenism metabolism, Ovary drug effects, Ovary metabolism, Proteolysis, Mice, Inbred C57BL, Young Adult, Adult, Rats, Sprague-Dawley, Artemisinins therapeutic use, Artemisinins pharmacology, Cholesterol Side-Chain Cleavage Enzyme metabolism, Cholesterol Side-Chain Cleavage Enzyme genetics, Mitochondrial Proteins metabolism, Mitochondrial Proteins genetics, Polycystic Ovary Syndrome drug therapy, ATP-Dependent Proteases genetics, ATP-Dependent Proteases metabolism
- Abstract
Polycystic ovary syndrome (PCOS), a prevalent reproductive disorder in women of reproductive age, features androgen excess, ovulatory dysfunction, and polycystic ovaries. Despite its high prevalence, specific pharmacologic intervention for PCOS is challenging. In this study, we identified artemisinins as anti-PCOS agents. Our finding demonstrated the efficacy of artemisinin derivatives in alleviating PCOS symptoms in both rodent models and human patients, curbing hyperandrogenemia through suppression of ovarian androgen synthesis. Artemisinins promoted cytochrome P450 family 11 subfamily A member 1 (CYP11A1) protein degradation to block androgen overproduction. Mechanistically, artemisinins directly targeted lon peptidase 1 (LONP1), enhanced LONP1-CYP11A1 interaction, and facilitated LONP1-catalyzed CYP11A1 degradation. Overexpression of LONP1 replicated the androgen-lowering effect of artemisinins. Our data suggest that artemisinin application is a promising approach for treating PCOS and highlight the crucial role of the LONP1-CYP11A1 interaction in controlling hyperandrogenism and PCOS occurrence.
- Published
- 2024
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