Lutenizing Hormone/ Chorionic Gonadotropin Receptors (LHCGR) are essential for follicular response to gonadotrophins. Following prolonged agonist stimulation, LHCGR desensitize through internalization and down-regulation. This prevents gonadotrophin hyper-sensitivity and may act as a protective mechanism against ovarian hyper-stimulation in women with polycystic ovarian syndrome (PCOS). The aim of our research in collaboration with Dr Venkateswarlu Kanarmarlapudi from Swansea Universityis to investigate the involvement of small GTP binding proteins on the internalization of LHCGR in human granulosa cells isolated from normal women and patients with PCOS. Our ongoing studies suggests that the small GTP protein ARF6 plays an important role in agonist-induced LHCGR internalization and response to gonadotrophins and that PCOS granulosa cells may have altered mechanisms.