Emerging role of GIP and related gut hormones in fertility and PCOS

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2020-03, Vol.125, p.170233, Article 170233
• Main Authors: Moffett, R. Charlotte, Naughton, Violetta
• Format: Article
• Language: English
• Subjects: 11-beta-HSD-1; Female; Gastric Inhibitory Polypeptide - pharmacology; Gastrointestinal Hormones - pharmacology; Ghrelin; GIP; GLP-1; Humans; Incretins - pharmacology; Infertility - drug therapy; Infertility - metabolism; Infertility - pathology; Insulin resistance; PCOS; Polycystic Ovary Syndrome - drug therapy; Polycystic Ovary Syndrome - metabolism; Polycystic Ovary Syndrome - pathology; PYY; RYGB
• ISSN: 0196-9781; 1873-5169; 1873-5169
• DOI: 10.1016/j.peptides.2019.170233

•Infertility associated with gross obesity and PCOS is alleviated by bariatric surgery.•Surgical-induced changes in circulating gut hormones may play a significant role in restoration of fertility.•GIP and GLP-1 receptors are present on pituitary, ovaries and testes, suggesting direct actions in addition to indirect effects through alleviation of insulin resistance.•Emerging evidence suggests that GIP and related gut hormones play a role in fertility and may provide a novel therapeutic pathway for reproductive disorders. Gastric inhibitory polypeptide (GIP) is best known as an incretin hormone released by enteroendocrine K-cells in response to feeding and stimulates insulin release to regulate blood glucose and nutrient homeostasis. More recently GIP has been ascribed a positive role in lipid metabolism, bone strength, cardiovascular function and cognition. The present paper considers an emerging role of GIP and related gut hormones in fertility and especially polycystic ovarian syndrome (PCOS). Key evidence concerns restoration of fertility in women with gross obesity and PCOS following bariatric surgery. This is considered to reflect indirect effects mediated by alleviation of insulin resistance together with possible direct effects of surgically induced changes of GIP, GLP-1 and related peptide hormones on ovaries and the hypothalamic-pituitary-adrenal axis. Further studies are required to determine inter-relationships between the hormones and cellular mechanisms involved but these observations suggest that GIP and other gut may provide a novel therapeutic approach for PCOS and other reproductive disorders.