Kem David C, Li Hongliang, Yu Xichun, Weedin Elizabeth, Reynolds Anna C, Forsythe Elizabeth, Beel Marci, Fischer Hayley, Hines Brendon, Guo Yankai, Deng Jielin, Liles Jonathan T, Nuss Zachary, Elkosseifi Myriam, Aston Christopher E, Burks Heather R, Craig LaTasha B
Section of Endocrinology and Diabetes, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma city, Oklahoma.
VA Medical Center, Oklahoma City, Oklahoma.
J Endocr Soc. 2020 Jun 18;4(8):bvaa078. doi: 10.1210/jendso/bvaa078. eCollection 2020 Aug 1.
Is polycystic ovary syndrome (PCOS) associated with activating autoantibodies (AAb) to the second extracellular loop (ECL2) of gonadotropin-releasing hormone receptor (GnRHR)?
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.
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).
GnRHR-ECL2-AAb are significantly elevated in patients with PCOS compared with NCs. Their presence raises important etiological, diagnostic, and therapeutic implications.
多囊卵巢综合征（PCOS）是否与促性腺激素释放激素受体（GnRHR）第二个细胞外环（ECL2）的激活自身抗体（AAb）有关？
我们采用酶联免疫吸附测定（ELISA）法，回顾性筛查了40例PCOS患者和14例月经规律的正常对照（NC）者的血清，以检测GnRHR - ECL2 - AAb的存在情况。我们从40例非PCOS排卵但不孕患者中获取了类似数据，作为感兴趣的对照组（OIC）。我们使用基于细胞的GnRHR生物测定法分析了纯化免疫球蛋白（Ig）G中的GnRHR - ECL2 - AAb活性。
PCOS组的平均ELISA值显著高于NC组（P = 0.000036）和OIC组（P = 0.0028）。与5例OIC受试者的样本相比，5例PCOS受试者样本中的IgG显示出GnRHR刺激活性呈剂量依赖性增加，在质量上类似于天然配体GnRH和合成激动剂亮丙瑞林的急性作用。GnRHR拮抗剂西曲瑞克显著抑制（P < 0.01）了7例PCOS患者IgG诱导的GnRHR活性升高，而7例OIC受试者的IgG活性水平未改变。其他5例OIC受试者的ELISA值相对较高，处于或高于95%置信限。进一步研究发现，3例活性正常或较低，2例IgG诱导的GnRHR活性升高。1例被西曲瑞克抑制，另1例未被抑制。PCOS IgG的共同存在增加了对GnRH的反应性，并使剂量反应曲线向左移动（P < 0.01）。
与NC相比，PCOS患者中GnRHR - ECL2 - AAb显著升高。它们的存在引发了重要的病因、诊断和治疗意义。
