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A Hyperandrogenic Mouse Model to Study Polycystic Ovary Syndrome
Published on: October 2, 2018
Curcumin Alleviates Hyperandrogenism and Promotes Follicular Proliferation in Polycystic Ovary Syndrome Rats:
Luo Zheng1, Pei-Fang Chen1, Wei-Chao Dai1
1Department of Gynecology and Obstetrics, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
Objective:
To explore the effect of curcumin on the insulin receptor substrate 1 (IRS1)/phosphatidylinositol-3-kinase (PI3K)/endometrial expression of glucose 4 (GLUT4) signalling pathway and its regulator, phosphatase and tensin homolog (PTEN), in a rat model of polycystic ovarian syndrome (PCOS).
Methods:
PCOS model was induced by letrozole intragastric administration. Sprague-Dawley rats were randomized into 4 groups according to a random number table: (1) control group; (2) PCOS group, which was subjected to PCOS and received vehicle; (3) curcumin group, which was subjected to PCOS and treated with curcumin (200 mg/kg for 2 weeks); and (4) curcumin+LY294002 group, which was subjected to PCOS, and treated with curcumin and LY294002 (a specific PI3K inhibitor). Serum hormone levels (17 β-estradiol, follicle stimulating hormone, luteinizing hormone, progesterone, and testosterone) were measured by enzyme linked immunosorbent assay, and insulin resistance (IR) was assessed using the homeostasis model assessment of IR. Ovarian tissues were stained with haematoxylin and eosin for pathological and apoptosis examination. Expression levels of key transcriptional regulators and downstream targets, including IRS1, PI3K, protein kinase B (AKT), GLUT4, and PTEN, were measured via reverse transcription polymerase chain reaction and Western blot, respectively.
Results:
The PCOS group showed impaired ovarian morphology and function. Compared with the PCOS group, curcumin treatment exerted ovarioprotective effects, down-regulated serum testosterone, restored IR, inhibited inflammatory cell infiltration in ovarian tissues, decreased IRS1, PI3K, and AKT expressions, and up-regulated GLUT4 and PTEN expressions in PCOS rats (P<0.05 or P<0.01). In contrast, IRS1, PI3K, AKT, and PTEN expression levels were not significantly different between PCOS and curcumin+LY294002 groups (P>0.05).
Conclusion:
The beneficial effects of curcumin on PCOS rats included the alteration of serum hormone levels and recovery of morphological ovarian lesions, in which, PTEN, a new target, may play a role in regulating the IRS1/PI3K/GLUT4 pathway.
Insights
Curcumin treatment improved polycystic ovarian syndrome (PCOS) in rats by restoring hormone levels and ovarian function. It regulated the insulin receptor substrate 1 (IRS1)/phosphatidylinositol-3-kinase (PI3K)/glucose transporter 4 (GLUT4) pathway, with phosphatase and tensin homolog (PTEN) potentially playing a key role.
Area of Science:
- Endocrinology and Reproductive Biology
- Molecular Signaling Pathways
- Pharmacology
Background:
- Polycystic ovarian syndrome (PCOS) is a complex endocrine disorder characterized by hormonal imbalances and insulin resistance.
- The insulin receptor substrate 1 (IRS1)/phosphatidylinositol-3-kinase (PI3K)/glucose transporter 4 (GLUT4) pathway is crucial for glucose metabolism and insulin sensitivity.
- Phosphatase and tensin homolog (PTEN) acts as a key regulator within this signaling cascade.
Purpose of the Study:
- To investigate the therapeutic effects of curcumin on a letrozole-induced rat model of PCOS.
- To elucidate curcumin's impact on the IRS1/PI3K/GLUT4 signaling pathway and its regulator, PTEN, in PCOS.
- To assess changes in serum hormone levels, insulin resistance, and ovarian morphology following curcumin treatment.
Main Methods:
- A PCOS rat model was established using letrozole administration.
- Rats were divided into control, PCOS, curcumin-treated PCOS, and curcumin + PI3K inhibitor (LY294002) treated PCOS groups.
- Hormone levels, insulin resistance (HOMA-IR), ovarian histology, and protein/gene expression of IRS1, PI3K, AKT, GLUT4, and PTEN were analyzed.
Main Results:
- Curcumin treatment significantly improved ovarian morphology and function in PCOS rats.
- Curcumin administration normalized serum testosterone levels, reduced insulin resistance, and inhibited ovarian inflammation.
- Curcumin upregulated GLUT4 and PTEN expression while downregulating IRS1, PI3K, and AKT expression in PCOS rats.
Conclusions:
- Curcumin demonstrates significant ovarioprotective effects in a PCOS rat model.
- Curcumin modulates key components of the IRS1/PI3K/GLUT4 signaling pathway.
- PTEN emerges as a potential therapeutic target for regulating this pathway in PCOS.
