The Role of GnRH Receptor Autoantibodies in Polycystic Ovary Syndrome

Overview

Journal J Endocr Soc

Specialty Endocrinology

Date 2020 Aug 18

PMID 32803090

Citations 8

Authors

David C Kem

Hongliang Li

Xichun Yu

Elizabeth Weedin

Anna C Reynolds

Elizabeth Forsythe

Marci Beel

Hayley Fischer

Brendon Hines

Yankai Guo

Jielin Deng

Jonathan T Liles

Zachary Nuss

Myriam Elkosseifi

Christopher E Aston

Heather R Burks

LaTasha B Craig

Affiliations

Soon will be listed here.

Abstract

Objective: Is polycystic ovary syndrome (PCOS) associated with activating autoantibodies (AAb) to the second extracellular loop (ECL2) of gonadotropin-releasing hormone receptor (GnRHR)?

Design And Methods: We retrospectively screened sera from 40 patients with PCOS and 14 normal controls (NCs) with regular menses using enzyme-linked immunosorbent assay (ELISA) for the presence of GnRHR-ECL2-AAb. We obtained similar data from 40 non-PCOS ovulatory but infertile patients as a control group (OIC) of interest. We analyzed GnRHR-ECL2-AAb activity in purified immunoglobulin (Ig)G using a cell-based GnRHR bioassay.

Results: The mean ELISA value in the PCOS group was markedly higher than the NC ( = .000036) and the OIC ( = .0028) groups. IgG from a sample of 5 PCOS subjects, in contrast to a sample of 5 OIC subjects, demonstrated a dose-dependent increase in GnRHR-stimulating activity qualitatively similar to the acute action of the natural ligand GnRH and the synthetic agonist leuprolide. The GnRHR antagonist cetrorelix significantly suppressed ( < .01) the elevated GnRHR activity induced by IgG from 7 PCOS patients while the IgG activity level from 7 OIC subjects was unchanged. Five other OIC subjects had relatively high ELISA values at or above the 95% confidence limits. On further study, 3 had normal or low activity while 2 had elevated IgG-induced GnRHR activity. One suppressed with cetrorelix while the other did not. The copresence of PCOS IgG increased the responsiveness to GnRH and shifted the dosage response curve to the left ( < .01).

Conclusions: GnRHR-ECL2-AAb are significantly elevated in patients with PCOS compared with NCs. Their presence raises important etiological, diagnostic, and therapeutic implications.

Citing Articles

Polycystic ovary syndrome.

Stener-Victorin E, Teede H, Norman R, Legro R, Goodarzi M, Dokras A Nat Rev Dis Primers. 2024; 10(1):27.

PMID: 38637590 DOI: 10.1038/s41572-024-00511-3.

The role of B cells in immune cell activation in polycystic ovary syndrome.

Ascani A, Torstensson S, Risal S, Lu H, Eriksson G, Li C Elife. 2023; 12.

PMID: 37401759 PMC: 10359092. DOI: 10.7554/eLife.86454.

Autoimmunity to the Follicle-Stimulating Hormone Receptor (FSHR) and Luteinizing Hormone Receptor (LHR) in Polycystic Ovarian Syndrome.

Schniewind H, Sattler L, Haudum C, Munzker J, Minich W, Obermayer-Pietsch B Int J Mol Sci. 2021; 22(24).

PMID: 34948471 PMC: 8706343. DOI: 10.3390/ijms222413667.

GnRH receptor-activating autoantibodies in polycystic ovary syndrome: identification of functional epitopes and development of epitope mimetic inhibitors.

Li H, Guo Y, Deng J, Gali H, Weedin E, Burks H Endocrine. 2021; 75(3):959-963.

PMID: 34807394 PMC: 8891032. DOI: 10.1007/s12020-021-02944-2.

Elevated activity levels of activating autoantibodies to the GnRH receptor in patients with polycystic ovary syndrome.

Weedin E, Burks H, Yu X, Li H, Aston C, Kem D F S Rep. 2021; 1(3):299-304.

PMID: 34223260 PMC: 8244267. DOI: 10.1016/j.xfre.2020.09.015.

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