Abstract
Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease. PCOS patients are characterized by hyperandrogenemia, anovulation, and metabolic dysfunction. Hypothalamus–pituitary–ovary axis imbalance is considered as an important pathophysiology underlying PCOS, indicating that central modulation, especially the abnormal activation of hypothalamic GnRH neurons plays a vital role in PCOS development. Increased GnRH pulse frequency can promote LH secretion, leading to ovarian dysfunction and abnormal sex steroids synthesis. By contrast, peripheral sex steroids can modulate the action of GnRH neurons through a feedback effect, which is impaired in PCOS, thus forming a vicious cycle. Additionally, hypothalamic GnRH neurons not only serve as the final output pathway of central control of reproductive axis, but also as the central connection point where reproductive function and metabolic state inter-regulate with each other. Metabolic factors, such as insulin resistance and obesity in PCOS patients can regulate GnRH neurons activity, and ultimately regulate reproductive function. Besides, gut hormones act on both brain and peripheral organs to modify metabolic state. Gut microbiota disturbance is also related to many metabolic diseases and has been reported to play an essential part in PCOS development. This review concludes with the mechanism of central modulation and the interaction between neuroendocrine factors and reproductive or metabolic disorders in PCOS development. Furthermore, the role of the gut microenvironment as an important part involved in the abnormal neuronal–reproductive–metabolic circuits that contribute to PCOS is discussed, thus offering possible central and peripheral therapeutic targets for PCOS patients.
Highlights
Polycystic ovary syndrome (PCOS) is a common reproductive and endocrine disorder, affecting 6–10% women of reproductive age worldwide [1]
Rising pieces of evidence suggest the correlation between gut microbiota and PCOS [8, 9]; our studies demonstrated that the gut microbiota–bile acid–IL-22 axis is involved in PCOS development via the crosstalk of gut innate immune system and ovary function [9, 10], providing strong evidence for the contribution of the gut microbiota in PCOS pathogenesis, while other possible pathways involved in gut microbiota need to be further explored
Kisspeptin and g-aminobutyric acid (GABA) are involved in the upstream regulation of Gonadotropinreleasing hormone (GnRH) neurons activity, which forms the final common pathway of central regulation of PCOS development
Summary
Hypothalamus–pituitary–ovary axis imbalance is considered as an important pathophysiology underlying PCOS, indicating that central modulation, especially the abnormal activation of hypothalamic GnRH neurons plays a vital role in PCOS development. Hypothalamic GnRH neurons serve as the final output pathway of central control of reproductive axis, and as the central connection point where reproductive function and metabolic state interregulate with each other. Metabolic factors, such as insulin resistance and obesity in PCOS patients can regulate GnRH neurons activity, and regulate reproductive function.
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