Comparison of immunocytochemical and molecular features with the phenotype in a case of incomplete male pseudohermaphroditism associated with a mutation of the luteinizing hormone receptor
Comparison of immunocytochemical and molecular features with the phenotype in a case of incomplete male pseudohermaphroditism associated with a mutation of the luteinizing hormone receptor
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DOI：
10.1210/jc.82.7.2159
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发表时间：
1997-07-01
影响因子：
5.8
通讯作者：
Bougneres, P
中科院分区：
文献类型：
--
作者：
Misrahi, M;Meduri, G;Bougneres, P
我们报道了一名婴儿出生时就出现与尿道下裂相关的阴茎发育不全的病例。睾酮生成量低、类固醇前体血清水平正常以及 LH 释放激素响应增加的 LH 均支持 Leydig 细胞分化或功能缺陷。睾丸的常规显微镜研究显示间质中有成纤维细胞。然而，使用抗 LH 受体和抗 P450c17 抗体的免疫细胞化学分析表明，这些细胞中约三分之一是 Leydig 细胞或 Leydig 细胞的前体。没有组织学特征可以将后者细胞与成纤维细胞区分开。在受体的胞外域中发现了半胱氨酸 133 对精氨酸的纯合取代。这是在 LH 受体胞外域中发现的第一个自然发生的错义突变。转染突变受体的 COS-7 细胞表现出 hCG 结合的明显损害，而在高 hCG 浓度下可以观察到一些 cAMP 的产生。我们认为 LH 受体功能的部分损伤（如 Leydig 细胞的存在所反映的）是导致我们患者中观察到的不完全男性假两性畸形的原因。
We report the case of an infant who presented at birth with a hypoplastic phallus associated with hypospadias. Low testosterone production, normal serum levels of steroid precursors, and increased LH in response to LH-releasing hormone supported a defect in Leydig cell differentiation or function. Conventional microscopic study of the testes showed fibroblastic cells in the interstitium. However, immunocytochemical analysis using anti-LH receptor and anti-P450c17 antibodies demonstrated that about one third of these cells were Leydig cells or precursors of Leydig cells. No histological feature could distinguish the latter cells from fibroblasts. A homozygous substitution of cysteine 133 for arginine was found in the extracellular domain of the receptor. This is the first naturally occurring missense mutation found in the extracellular domain of the LH receptor. COS-7 cells transfected with the mutant receptor exhibited a marked impairment of hCG binding, whereas some cAMP production could be observed at high hCG concentrations. We propose that the partial impairment of LH receptor function, as reflected by the presence of Leydig cells, was responsible for the incomplete male pseudohermaphroditism observed in our patient.