Presence and absence of follicle-stimulating hormone receptor mutations provide some insights into spontaneous ovarian hyperstimulation syndrome physiopathology
Presence and absence of follicle-stimulating hormone receptor mutations provide some insights into spontaneous ovarian hyperstimulation syndrome physiopathology
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DOI：
10.1210/jc.2005-1580
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发表时间：
2006-02-01
影响因子：
5.8
通讯作者：
Costagliola, S
中科院分区：
文献类型：
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作者：
De Leener, A;Montanelli, L;Costagliola, S
背景：卵巢过度刺激综合征（OHSS）是卵巢刺激治疗的一种潜在的危及生命的并发症。此外，最近在妊娠早期出现自发性OHSS（sOHSS）且人绒毛膜促性腺激素（hCG）水平正常的患者中描述了FSH受体（FSHr）的四种突变。本研究的目的是在与不同水平的hCG和TSH相关的sOHSS患者中寻找新的FSHr突变，以1）发现对FSHr活化和特异性重要的新残基，和2）更好地描绘sOHSS的不同表现的病理生理学。设计、干预和患者：在血液取样后，我们对来自8名患有sOHSS的患者的基因组白细胞DNA的FSHr进行测序，这些患者来自妊娠的第一或第二三个月，具有正常或高hCG水平或具有与严重甲状腺功能减退相关的高TSH水平。设定：本研究是在一所大学的实验室进行的。主要结果测量：主要结果测量是FSHr测序和体外评估的变化的cAMP生产的FSHr突变体。结果：一个新的突变被发现在患者的sOHSS的妊娠早期与正常的hCG水平：I5.54（545）T，在跨膜螺旋V的FSHr。功能测试时，该突变体显示混杂激活hCG和TSH与可检测的组成型活性。相比之下，没有突变被发现在FSHr高hCG或TSH水平的患者，这表明，对于这7名患者，sOHSS结果从野生型FSHr非常高浓度的hCG或TSH.Conclusions的自然混杂刺激：sOHSS可以发生至少三种不同的病理生理机制。
Context: Ovarian hyperstimulation syndrome ( OHSS) is a potentially life-threatening complication of ovarian stimulation treatments. Moreover, four mutations of the FSH receptor (FSHr) were recently described in patients presenting with spontaneous OHSS (sOHSS) of the first trimester of pregnancy with normal levels of human chorionic gonadotropin (hCG).Objective: The objective of this study was to look for novel FSHr mutations in patients with sOHSS associated with different levels of hCG and TSH to 1) find new residues important for FSHr activation and specificity, and 2) better delineate the pathophysiology of the different presentations of sOHSS.Design, Intervention, and Patients: After blood sampling, we sequenced the FSHr from genomic leukocytes DNA from eight patients with sOHSS of the first or second trimester of pregnancy with normal or high hCG levels or with high TSH levels associated with severe hypothyroidism. Setting: This study was performed at a university laboratory.Main Outcome Measure: The main outcome measure was FSHr sequencing and in vitro evaluation of the variation of cAMP production of FSHr mutants.Results: A new mutation was found in the patient with sOHSS of the first trimester of pregnancy with a normal hCG level: I5.54(545)T, in transmembrane helix V of the FSHr. When tested functionally, this mutant displayed promiscuous activation by both hCG and TSH together with detectable constitutive activity. In contrast, no mutations were found in the FSHr from patients with high hCG or TSH levels, indicating that for those seven patients, sOHSS results from the natural promiscuous stimulation of a wild-type FSHr by very high concentrations of hCG or TSH.Conclusions: sOHSS can occur by at least three different pathophysiological mechanisms.