Chinese scholars make progress in polycystic ovarian syndrome treatment
Figure. Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction
Supported by the National Natural Science Foundation of China (Grant No. 82170884, 81730021, and 81601251), Prof. Qi-qun Tang’s research group from Fudan University made progress in polycystic ovarian syndrome treatment. The related research was titled “Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction” and published in Science on June 14, 2024.
Article link:https://www.science.org/doi/10.1126/science.adk5382.
Polycystic ovarian syndrome (PCOS) is a complicated reproductive-metabolic disease and one of the most common endocrine disorders affecting women of reproductive age, with a global prevalence of 10-13%. Androgen excess is the main driver of numerous phenotypic features of PCOS, such as follicular dysplasia, impaired ovulation, endometrial diseases and metabolic dysfunction.
This study shows that artemisinins exhibit considerable improvements in hyperandrogenemia, irregular estrous cycles, polycystic ovarian morphology, and low fertility in the PCOS-like rodent models. Artemisinins inhibit hyperandrogenemia by repressing ovarian testosterone synthesis. Quantitative proteomics analysis reveals CYP11A1, the enzyme catalyzing the initial step of androgen synthesis, as the most significantly decreased protein affected by artemisinins. Further investigation shows that artemisinins induce the degradation of CYP11A1, leading to the inhibition of ovarian androgen synthesis. This inhibitory effect is diminished in the absence of CYP11A1. Mechanistically, artemisinins directly target the protease LONP1, enhancing the interaction between LONP1 and CYP11A1 and promoting the LONP1-catalyzed degradation of CYP11A1. Finally, a pilot clinical trial is conducted to confirm the therapeutic effects of artemisinins in patients with PCOS. (see Figure)
This study suggests that artemisinin application is a promising approach for treating PCOS and highlights the crucial role of the LONP1-CYP11A1 interaction in controlling hyperandrogenism and PCOS occurrence.
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