Endocrine Abstracts

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women of reproductive age and, accounts for 80% of the causes of anovulatory infertility. Despite PCOS being often associated with obesity and insulin-resistance, these are not invariably present. As PCOS aetiology and underlying mechanisms remain unclear, clinical management is limited to target symptoms. Recent evidence suggested the potential of GLP-1 receptor agonists therapies in ameliorating PCOS endocrine and reproductive manifestations, in parallel to inducing weight loss and improving dysglycemia. Moreover, a dual GLP-1/GIP co-agonist drug with even more promising results was just rendered available. Notably, no previous study has been conducted to identify incretin receptors in the human ovary. Herein we aimed to investigate the presence of gastric inhibitory polypeptide (GIP) and glucagon-like-peptide-1 (GLP-1) receptors in human granulosa cells to understand the role of incretin hormones in ovarian physiology and to assess the potential use of incretin-based drugs for the treatment of PCOS-related infertility. For the first time, we were able to identify the presence of GIP receptor transcripts in cumulus cells from patients with and without PCOS undergoing fertility treatments. Additionally, the presence of the GIP receptor was also found on non-luteinized granulosa cells (HGrC1) and granulosa tumour cells (COV434). On the other hand, we were unable to detect the GLP-1 receptor in granulosa cells. Further studies are needed to evaluate whether there are differences in the expression levels of GIP receptors in granulosa cells from overweight/non-overweigh women with PCOS and overweight/non-overweight normo-ovulatory women. Overall, our preliminary findings suggest that GIP may have a significant role in modulating female reproductive function which may provide future targets for pharmacological intervention in reproductive disorders.