Gordon, Uma D

Kanamarlapudi, Venkateswarlu

López Bernal, Andrés

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

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                          Kanamarlapudi, V., Gordon, U. D., & López Bernal, A. (2016). Luteinizinghormone/chorionic gonadotrophin receptor overexpressed in granulosa cellsfrom polycystic ovary syndrome ovaries is functionally active. ReproductiveBioMedicine Online, 32(6), 635-641. DOI: 10.1016/j.rbmo.2016.03.003Peer reviewed versionLicense (if available):CC BY-NC-NDLink to published version (if available):10.1016/j.rbmo.2016.03.003Link to publication record in Explore Bristol ResearchPDF-documentThis is the author accepted manuscript (AAM). The final published version (version of record) is available onlinevia Elsevier at http://www.sciencedirect.com/science/article/pii/S147264831630027X. Please refer to anyapplicable terms of use of the publisher.University of Bristol - Explore Bristol ResearchGeneral rightsThis document is made available in accordance with publisher policies. Please cite only the publishedversion using the reference above. Full terms of use are available:http://www.bristol.ac.uk/pure/about/ebr-terms.htmlFig 185 kDa55 kDa-tubulinLHCGRNormalPCOSABNormal PCOS0123***Relative LHCGR proteinexpression (fold)B0 15 30 45 600.02.55.07.510.012.5******* ***NormalPCOSTime (min)cAMP accumulation(Fold over basal)A0 1 2 3051015*** ***PCOSNormalLog [HCG] IU/mlcAMPaccumulation(Fold over basal)Fig 2A-tubulinARF1ARF6NormalPCOS1.0 0.971.0 1.74BTotal ARF6ARF6-GTP(i)HCG        - +        - + (10IU/ml) (ii)Normal PCOS012345*******ARF6-GTP levels(fold over basal)Fig 3NormalPCOSHCG          - +        +        +       +(10IU/ml) C012345678+ Myr-ARF1p (2.5M)+ Myr-ARF6p (2.5M)No peptide+Penetratin (2.5M)***** * *cAMP accumulation (Fold over basal)0.02.55.07.510.012.515.017.5+ Myr-ARF1p (2.5M)+ Myr-ARF6p (2.5M)No peptide+Penetratin (2.5M)*** *** *****cAMP accumulation (Fold over basal)Fig 4HCG        - +       +      +        +(10IU/ml) NormalPCOSD051015+BFA (10g/ml)No inhibitor+DMSO (0.2%)+SecinH3 (15M)*** *** ******cAMP accumulation (Fold over basal)0.02.55.07.5+BFA (10g/ml)No inhibitor+DMSO (0.2%)+SecinH3 (15M)*** ** ******cAMP accumulation (Fold over basal)

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

https://research-information.bristol.ac.uk/files/81002394/RBMO_D_15_00322_revised_manuscript.pdf

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

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