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Curcumin Alleviates Hyperandrogenism and Promotes Follicular Proliferation in Polycystic Ovary Syndrome Rats: Insights on IRS1/PI3K/GLUT4 and PTEN Modulations

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Abstract

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.

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Fujian Medical University Union Hospital, Fuzhou, 350001, China

    Luo Zheng, Pei-fang Chen, Wei-chao Dai, Zhi-qun Zheng & Hui-lan Wang

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  1. Luo Zheng
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  2. Pei-fang Chen
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  3. Wei-chao Dai
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  4. Zhi-qun Zheng
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  5. Hui-lan Wang
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Contributions

Wang HL designed the study, participated in its coordination and helped to draft the manuscript. Zheng L, Chen PF, Dai WC and Zheng ZQ performed the experiments, performed the statistical analyses and drafted the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Hui-lan Wang.

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Conflict of Interest

The authors declare no conflicts of interest in this work.

Supported by the Joint Funds for Innovation of Science and Technology of Fujian Province (No. 2018Y9046) and the Qihang Foundation Project of Fujian Medical University of China (No. 2018QH1023)

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Zheng, L., Chen, Pf., Dai, Wc. et al. Curcumin Alleviates Hyperandrogenism and Promotes Follicular Proliferation in Polycystic Ovary Syndrome Rats: Insights on IRS1/PI3K/GLUT4 and PTEN Modulations. Chin. J. Integr. Med. 28, 1088–1095 (2022). https://doi.org/10.1007/s11655-022-3582-z

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  • DOI: https://doi.org/10.1007/s11655-022-3582-z

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