新促卵泡激素受体的自然灭活突变:受体功能和表型之间的相关性。
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都兰P,博我,Gougeon Meduri G, Desroches, Pichard C, Detoeuf M, Paniel B, Prieur M,左恩JR:米格罗姆E, F Kuttenn, Misrahi M
新促卵泡激素受体的自然灭活突变:受体功能和表型之间的相关性。
摩尔性。1999年11月,13 (11):1844 - 54。
- PubMed ID
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10551778 (在PubMed]
- 文摘
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卵巢功能早衰发生在几乎1%的妇女在40岁以下。分子改变的卵泡刺激素受体(FSHR)最近被描述。第一次FSHR被确认在芬兰的纯合子突变。最近,我们描述了两个新的突变的FSHR女人展示部分FSH-resistance综合症(病人1)。我们现在报告的新分子改变FSHR(病人2)在另一个女人在19岁的原发性闭经对比与正常青春期发育。她高血浆FSH,大量卵泡3毫米大小超声都证明了这一点。组织学和免疫组织化学检查卵巢活检显示正常的卵泡发育起来的存在进一步窦的阶段和破坏阶段。DNA测序显示两个的杂合突变:Asp224Val在细胞外的域和Leu601Val FSHR第三细胞外循环。细胞转染和表达向量编码野生型和突变Leu601Val受体结合激素相似的亲和力,而绑定与Asp224Val几乎没有检测到突变体。共焦显微镜显示,后者有一个针对受损细胞膜。这证实了它的积累作为mannose-rich前体。 Adenylate cyclase stimulation by FSH of the Leu601Val mutant receptor showed a 12+/-3% residual activity, whereas in patient 1 a 24+/-4% residual activity was detected for the Arg573Cys mutant receptor. These results are in keeping with the fact that estradiol and inhibin B levels were higher in patient 1 and that stimulation with recombinant FSH did not increase follicular size, estradiol, or inhibin B levels in patient 2 in contrast to what was observed for patient 1. Thus, differences in the residual activity of mutated FSHR led to differences in the clinical, biological, and histological phenotypes of the patient.