Neuroendocrine Determinants of Polycystic Ovary Syndrome

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women and a major cause of anovulatory infertility. A diagnosis of PCOS is established based the presence of two out of three clinical symptoms, which are criteria accepted by the ESHRE/ASRM (European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine). Gonadotropin-releasing hormone (GnRH) is responsible for the release of luteinizing hormone, and follicle stimulating hormone from the pituitary and contributes a leading role in controlling reproductive function in humans. The goal of this review is to present the current knowledge on neuroendocrine determinations of PCOS. The role of such neurohormones as GnRH, and neuropeptides kisspeptin, neurokinin B, phoenixin-14, and galanin is discussed in this aspect. Additionally, different neurotransmitters (gamma-aminobutyric acid (GABA), glutamate, serotonin, dopamine, and acetylcholine) can also be involved in neuroendocrine etiopathogenesis of PCOS. Studies have shown a persistent rapid GnRH pulse frequency in women with PCOS present during the whole ovulatory cycle. Other studies have proved that patients with PCOS are characterized by higher serum kisspeptin levels. The observations of elevated serum kisspeptin levels in PCOS correspond with the hypothesis that overactivity in the kisspeptin system is responsible for hypothalamic-pituitary-gonadal axis overactivity. In turn, this causes menstrual disorders, hyperandrogenemia and hyperandrogenism. Moreover, abnormal regulation of Neurokinin B (NKB) is also suspected of contributing to PCOS development, while NKB antagonists are used in the treatment of PCOS leading to reduction in Luteinizing hormone (LH) concentration and total testosterone concentration. GnRH secretion is regulated not only by kisspeptin and neurokinin B, but also by other neurohormones, such as phoenixin-14, galanin, and Glucagon-like peptide-1 (GLP-1), that have favorable effects in counteracting the progress of PCOS. A similar process is associated with the neurotransmitters such as GABA, glutamate, serotonin, dopamine, and acetylcholine, as well as the opioid system, which may interfere with secretion of GnRH, and therefore, influence the development and severity of symptoms in PCOS patients. Additional studies are required to explain entire, real mechanisms responsible for PCOS neuroendocrine background.

Effect of metformin versus metformin plus liraglutide on gonadal and metabolic profiles in overweight patients with polycystic ovary syndrome

“…Patients with PCOS demonstrate increased levels of GnRH leading to a higher frequency of LH pulsation, stimulation of LH-mediated androgen production, and disruption of follicle development. The resulting chronic anovulation is due to the relatively low level of FSH that occurs secondary to the altered GnRH release pattern ( 29 ). Recent studies in induced rat models have shown the expression of GLP receptors in the hypothalamus, pituitary, the change of ovary during the ovulatory cycle.…”

Modified Banxia Xiexin Decoction Ameliorates Polycystic Ovarian Syndrome With Insulin Resistance by Regulating Intestinal Microbiota

“…IR is not merely an important pathophysiological change but also a vital hub connecting reproductive abnormalities and metabolic disorders of PCOS ( Carreau and Baillargeon, 2015 ). IR and its resulting compensatory hyperinsulinism are linked to hyperandrogenemia in various ways; for instance, they stimulate the pituitary to secrete luteinizing hormone (LH) ( Teede et al., 2007 ; Szeliga et al., 2022 ) and decrease hepatic production of sex hormone-binding globulin (SHBG) ( Calcaterra et al., 2021 ). It can also affect the metabolic function of the body by affecting the level of blood lipids and a variety of adipocytokines ( Teede et al., 2007 ; Zheng et al., 2017 ; Calcaterra et al., 2021 ).…”

Oxidative stress and antioxidant imbalance in ovulation disorder in patients with polycystic ovary syndrome

“…HA can stimulate the initiation of early follicular development by increasing the expression of IGF-1 receptor, resulting in excessive proliferation of antral follicles and an increase in the proportion of small follicles growing in the ovary ( 65 – 67 ). Hyperinsulinemia and/or high levels of LH synergistically improve the sensitivity of granulosa cells to LH, leading to premature differentiation of granulosa cells and an imbalance in LH/FSH levels, so that FSH deficiency destroys the choice of dominant follicles, leading to the accumulation of small antral follicles ( 68 , 69 ); at the same time, the premature response of small antral follicles to high LH promotes the early terminal differentiation of follicles ( 70 ). In the ovary, the proliferation and differentiation of granulosa cells play an important role in the development of follicles.…”