ESPEYB21 12. Type 2 Diabetes, Metabolic Syndrome and Lipids Metabolic Syndrome (3 abstracts)
12.11. Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction
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 & Tang QQ
Science. 2024 Jun 14;384(6701):eadk5382. doi:10.1126/science.adk5382.
Brief Summary: Artemisinins, compounds known for their antimalarial properties, suppress ovarian androgen synthesis by promoting degradation of cytochrome P450 11A1 (CYP11A1). Hence, they are a promising new approach for preventing and treating PCOS.
Comment: Polycystic ovary syndrome (PCOS), characterized by hyperandrogenism, chronic anovulation, and insulin resistance, is one of the most common reproductive endocrinopathies, affecting ~8-18% of reproductive-aged women.1 Despite its high prevalence, the pathogenesis remain poorly understood and current treatments are nonspecific, primarily targeting symptom relief.
Artemisinin and its semisynthetic derivatives, originally discovered by Tu Youyou in 1972, are used in the treatment of malaria caused by Plasmodium falciparum. Tu Youyou, was awarded the 2015 Nobel Prize in Physiology or Medicine for this discovery. Artemisinin is extracted from the herb Artemisia annua (sweet wormwood), which gained notoriety due to its use in absinthe, a favorite French liqueur2.
This study investigated the therapeutic potential of artemisinins in rodent models and human patients with PCOS, evaluating the effect of artemisinin derivatives on testosterone level, estrous cycle, and polycystic ovarian morphology. In rodent models, the artemisinin analogue artemether improved hyperandrogenemia, irregular estrous cycles, polycystic ovarian morphology, and low fertility. Artemisinins reduced hyperandrogenemia by inhibiting ovarian testosterone synthesis. The enzyme catalyzing the initial step of androgen synthesis is cytochrome P450 family 11 subfamily A member 1 (CYP11A1), which interacts with lon peptidase 1 (LONP1). Disruption of the interaction between LONP1 and CYP11A1 leads to the up regulation of CYP11A1, increasing androgen production and worsening PCOS. Artemisinins bind to LONP1, initiating interaction between LONP1 and CYP11A1, leading to degradation of CYP11A1, subsequently inhibiting ovarian androgen synthesis and curbing PCOS.
A pilot clinical trial was conducted to confirm the therapeutic effects of artemisinins in women with PCOS. Dihydroartemisinin reduced hyperandrogenemia, lowered anti-Müllerian hormone levels, improved polycystic ovarian morphology, and contributed to normalized menstrual cycles. A randomised controlled trial is now needed.
References: 1. Zhang J, Zhu Y, Wang J, Hu H, Jin Y, Mao X, Zhang H, Ye Y, Xin X, Li D. Global burden and epidemiological prediction of polycystic ovary syndrome from 1990 to 2019: A systematic analysis from the Global Burden of Disease Study 2019. PLoS One. 2024 Jul 18;19(7):e0306991. doi:10.1371/journal.pone.0306991.2. Lachenmeier DW, Walch SG, Padosch SA, Kröner LU. Absinthe–a review. Crit Rev Food Sci Nutr. 2006;46(5):365-77. doi:10.1080/10408690590957322. PMID: 16891209.
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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