hormone/chorionic gonadotrophin receptor overexpressed in granulosa cells from polycystic ovary syndrome ovaries is functionally active. Reproductive BioMedicine

Polycystic ovarian syndrome (PCOS) is associated with anovulatory infertility. Luteinizing hormone/chorionic gonadotropin receptor (LHCGR), which is critical for ovulation, has been suggested to be expressed prematurely in the ovarian follicles of women with PCOS. The objective of this study was to analyse the expression and activity of LHCGR in ovarian granulosa cells from PCOS patients and the involvement of ARF6 small GTPase in LHCGR internalisation. Granulosa cells (GCs) isolated from follicular fluid collected during oocyte retrieval from normal women (n=19) and women with PCOS (n=17) were used to study differences in LHCGR protein expression and activity between normal and PCOS patients. LHCGR expression is up-regulated in GCs from PCOS women. LHCGR in PCOS GCs is functionally active as evidenced by increased cAMP production upon human gonadotrophin (HCG)-stimulation. Moreover, ARF6 is highly expressed in GCs from PCOS patients and HCG-stimulation increases the levels of active ARF6. The inhibition of ARF6 activation attenuates HCG-induced LHCGR internalisation in both normal and PCOS GCs, indicating that there are no alterations in LHCGR internalisation in GCs from PCOS. In conclusion, the expression and activation of LHCGR and ARF6 are up-regulated in GCs from PCOS women but the mechanism of agonist-induced LHCGR internalisation is unaltered.