Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction.
Science
; 384(6701): eadk5382, 2024 Jun 14.
Article
in En
| MEDLINE
| ID: mdl-38870290
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polycystic Ovary Syndrome
/
Cholesterol Side-Chain Cleavage Enzyme
/
Mitochondrial Proteins
/
Artemisinins
/
ATP-Dependent Proteases
Limits:
Adult
/
Animals
/
Female
/
Humans
Language:
En
Journal:
Science
Year:
2024
Type:
Article
Affiliation country:
China