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Updated: Sep 28, 2025
Author Spotlight: Investigating the Mechanisms and Inducing Models of Polycystic Ovary Syndrome
Published on: July 5, 2024
Molecular docking and mouse modeling suggest CMKLR1 and INSR as targets for improving PCOS phenotypes by minocycline
Mahdie Kian1, Elham Hosseini2, Tooba Abdizadeh3
1Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Abstract:
Polycystic ovary syndrome (PCOS) is the most common cause of women's infertility. Some inflammatory pathways play a pivotal role in the pathogenesis of PCOS. This study aimed to investigate the possible beneficial effects of minocycline on chemokine-like receptor 1 (CMKLR1) and Insulin Receptor (INSR) in a PCOS model. A molecular docking study was implemented using Molecular Operating Environment (MOE) software. The PCOS was induced in NMRI mice (mean body weight 14.47±0.23) by 28 days estradiol valerate injection (2 mg/kg/day). The mice were then divided into six groups (n=8 per group, mean body weight 17.77± 0.26): control (received normal saline), PCOS model, control for minocycline, minocycline treated PCOS (50 mg/kg), letrozole treated PCOS (0.5 mg/kg), and metformin-treated PCOS (300 mg/kg). Serum FSH, LH, estradiol (E2), and testosterone were detected by ELISA. The ovarian tissues were stained by hematoxylin and eosin. The CMKLR1 and INSR expression levels were determined by Real-time-PCR. The molecular docking studies showed scores of -10.92 and -9.30 kcal/mol, respectively, for minocycline with CMKLR1 and INSR. Estradiol valerate treatment led to a significant increase in E2, graffian follicle, and decrease in corpus luteum (CL) numbers (P<0.05), while minocycline treatment improved these PCOS features. The minocycline treatment significantly decreased the CMKLR1 expression and increased the INSR expression (P<0.05) while the CMKLR1 expression was increased in PCOS model. Minocycline may improve ovulation in PCOS model by returning E2 to a normal level and increasing CL number (ovulation signs). These beneficial outcomes may be related to the changes in CMKLR1 and INSR gene expression involved in glucose metabolism and inflammation.
Insights
Minocycline shows promise in treating polycystic ovary syndrome (PCOS) by improving ovulation and restoring hormone balance. This study found minocycline effectively modulated chemokine-like receptor 1 (CMKLR1) and Insulin Receptor (INSR) gene expression in a PCOS mouse model.
Area of Science:
- Reproductive Endocrinology
- Pharmacology
- Molecular Biology
Background:
- Polycystic ovary syndrome (PCOS) is a leading cause of female infertility, often linked to inflammatory pathways.
- Understanding the molecular mechanisms underlying PCOS pathogenesis is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the potential therapeutic effects of minocycline on chemokine-like receptor 1 (CMKLR1) and Insulin Receptor (INSR) in a mouse model of PCOS.
- To evaluate minocycline's impact on hormonal balance, ovarian morphology, and gene expression related to inflammation and metabolism in PCOS.
Main Methods:
- A PCOS mouse model was established using estradiol valerate injection.
- Mice were treated with minocycline, letrozole, or metformin, alongside control and PCOS groups.
- Hormone levels (FSH, LH, E2, testosterone), ovarian histology, and CMKLR1/INSR gene expression (Real-time-PCR) were analyzed.
- Molecular docking simulations were performed to assess minocycline's binding affinity to CMKLR1 and INSR.
Main Results:
- Minocycline treatment reversed PCOS-induced increases in estradiol (E2) and graffian follicle count, while restoring corpus luteum (CL) numbers.
- In the PCOS model, CMKLR1 expression was elevated, whereas INSR expression was decreased; minocycline treatment normalized these levels.
- Molecular docking indicated favorable binding interactions between minocycline and both CMKLR1 (-10.92 kcal/mol) and INSR (-9.30 kcal/mol).
Conclusions:
- Minocycline demonstrates beneficial effects in a PCOS mouse model, potentially by modulating CMKLR1 and INSR gene expression.
- These improvements may be linked to minocycline's ability to restore normal E2 levels, increase CL formation, and influence pathways involved in glucose metabolism and inflammation.
- Minocycline represents a potential therapeutic agent for PCOS, warranting further investigation into its clinical efficacy.
