title: Luteinizing hormone/chorionic gonadotrophin receptor overexpressed in granulosa cells from polycystic ovary syndrome ovaries is functionally active.
abstract: Polycystic ovarian syndrome (PCOS) is associated with anovulatory infertility. Luteinizing hormone/chorionic gonadotrophin receptor (LHCGR), which is critical for ovulation, has been suggested to be expressed prematurely in the ovarian follicles of women with PCOS. This study aimed to analyse the expression and activity of LHCGR in ovarian granulosa cells from PCOS patients and the involvement of ARF6 small GTPase in LHCGR internalization. Granulosa cells (GC) 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 GC from PCOS women. LHCGR in PCOS GC is functionally active, as shown by increased cAMP production upon human gonadotrophin (HCG)-stimulation. Moreover, ARF6 is highly expressed in GC from PCOS patients and HCG-stimulation increases the concentrations of active ARF6. The inhibition of ARF6 activation attenuates HCG-induced LHCGR internalization in both normal and PCOS GC, indicating that there are no alterations in LHCGR internalisation in GC from PCOS. In conclusion, the expression and activation of LHCGR and ARF6 are up-regulated in GC from PCOS women but the mechanism of agonist-induced LHCGR internalization is unaltered.
authors.affiliation: Institute of Life Science 1, College of Medicine, Swansea University, Swansea, UK. Electronic address: k.venkateswarlu@swansea.ac.uk.
authors.forename: Venkateswarlu
authors.initials: V
authors.lastname: Kanamarlapudi
authors.affiliation: Bristol Centre for Reproductive Medicine, North Bristol NHS Trust, Southmead Hospital, Westbury-on-Trym, Bristol, UK.
authors.forename: Uma D
authors.initials: UD
authors.lastname: Gordon
authors.affiliation: Division of Obstetrics and Gynaecology, School of Clinical Sciences, University of Bristol, Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Bristol, UK.
authors.forename: Andrés
authors.initials: A
authors.lastname: López Bernal
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D006063:Chorionic Gonadotropin / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D015571:Follicular Fluid / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000737:chemistry; D006107:Granulosa Cells / Q000166:cytology*; D006801:Humans; D014975:Lutein / Q000737:chemistry; D007986:Luteinizing Hormone / Q000378:metabolism; D006080:Ovarian Follicle / Q000378:metabolism; D010053:Ovary / Q000378:metabolism; D010060:Ovulation / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D011974:Receptors, LH / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000089982:ADP-Ribosylation Factor 6; D006063:Chorionic Gonadotropin; D011974:Receptors, LH; D007986:Luteinizing Hormone; D000242:Cyclic AMP; D020558:GTP Phosphohydrolases; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human; D014975:Lutein
keywords: ARF6; LHCGR; PCOS; cAMP; human granulosa cells