Kisspeptin links chronic psychological stress to reproductive and metabolic dysfunction in PCOS patients and rat models

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterized by reproductive and metabolic abnormalities, often co-occurring with mental health issues. Current treatments primarily address symptoms, but the underlying pathophysiological mechanisms linking stress, metabolism, and reproduction remain unclear. Kisspeptin (Kiss1), a neuropeptide crucial for regulating the hypothalamic-pituitary-gonadal (HPG) axis and energy metabolism, is a candidate mediator. Understanding its role could reveal novel therapeutic targets for PCOS management.

This study investigated Kisspeptin's role in PCOS using both human and animal models. In 27 women with PCOS and 11 healthy controls, researchers measured fasting insulin (INS), blood glucose, serum Kiss1, and monoamine neurotransmitter levels. For animal experiments, 16 rats were divided into control, PCOS, chronic unpredictable mind stress (CUMS), and PCOS + CUMS groups. They assessed behavioral changes, reproductive endocrine function, glucose metabolism, ovarian granulosa cell apoptosis, and expression of Kiss1, Kiss1R, and GnRH in hypothalamic tissues, alongside IGF-1 and IGFBP-1 levels in ovarian tissues.

In women with PCOS, body mass index, fasting INS levels, HOMA-IR index, and serum Kiss1 levels were significantly elevated compared to healthy controls. Conversely, serum monoamine neurotransmitter levels were lower in PCOS patients. Crucially, Kiss1 levels negatively correlated with monoamine neurotransmitter concentrations and positively correlated with both INS levels and the HOMA-IR index, suggesting a direct link. > In the PCOS + CUMS model rats, researchers observed significant reproductive endocrine dysfunction, abnormal glucose metabolism, and depressive-like behaviors. These changes were accompanied by upregulated expression of Kiss1 and gonadotropin-releasing hormone (GnRH), downregulated IGF-1 levels, and increased ovarian granulosa cell apoptosis, further supporting Kisspeptin's role in mediating stress-induced PCOS pathology.