変異黄体化ホルモンの生殖機構に及ぼす影響と家族性遺伝に関する研究

突变黄体生成素对生殖机制及家族遗传影响的研究

• 批准号: 10671542
• 负责人: TAKAHASHI Kentaro
• 金额: $ 0.83万
• 依托单位: Shimane Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671542/
• 关键词: luteinizing hormone; β-subnit variant; gene analysis; immunoassays; ovulatory disorders; pituitary response; 早発閉経; 高プロラクチン血症; 黄体機能不全

Although polymorphism in the LHβ gene variant with a mutant β-subunit (Trp8 to Arg8 and Ile15 to Thr15) is commonly found in most population, the clinical consequences of carrying this LH variant are still unclear. To elucidate the effect of an luteinizing hormone (LH) variant on ovulation and reproductive mechanism and to evaluate its significance in gynecologic disease, including infertility, serum samples were collected from healthy non-pregnant Japanese women and patients with gynecologic disease and DNA from blood cells was studied in patients using polymerase chain reaction and direct sequencing. In immunoassays, results with a monoclonal antibody recognizing only the wild-type hormone (SPAC-S LH) and a polyclonal antibody recognizing the variant (Immulyze LH) as well were compared as a ratio (LH ratio : SPAC-S LH/Immulyze LH) and 0.50 was considered a "cut-off" value for identifying individuals with the variant. We conclude that measuring serum LH with specific immunoassay syste … More ms can distinguish subjects with variant from those with normal LH in screening for the mutant LHβ gene. Using the ratio of KH values from these assays to determine variant (<ィイD2-ィエD20.5) or wild-type (>0.5) LH status ratio, the variant occurred more frequently in the patients with gynecologic disease (18.4%) than in healthy women (8.5%). The variant was more frequent in patients with ovulatory disorders (43.8%) than other patients (16.0%). Premature ovarian failure, hyperprolactinemia and luteal insufficiency were significantly more frequent in patients with the variant. Variant LH may contribute to female reproductive disorder, including infertility and premature ovarian failure. To assess the secretion of variant LH on pituitary stimulation than wild-type LH, since in serum variant LH showed a more rapid increase and reached a higher apparent concentration than the wild-type hormone.Furethermore, we confirmed that subjects who were homozygous for mutant LHβ-subunit showed an excessive LH response in the GnRH stimulation test, similar to the response in patients with PCOS. However, this response pattern from variant LH did not show a relationship to ovulatory disorders. Therefore, the biologic effects and clinical significance of variant LH require much further investigation. Less

虽然在大多数人群中普遍发现LHβ基因变异体的多态性，但携带这种LH变异体的临床后果仍不清楚。为了阐明促黄体生成素（LH）变体对排卵和生殖机制的影响，并评估其在妇科疾病（包括不孕症）中的意义，收集了健康非妊娠日本妇女和妇科疾病患者的血清样本，并使用聚合酶链反应和直接测序研究了患者血细胞DNA。在免疫测定中，将仅识别野生型激素（SPAC-S LH）的单克隆抗体和也识别变体（Immulyze LH）的多克隆抗体的结果作为比率（LH比率：SPAC-S LH/Immulyze LH）进行比较，并将0.50视为鉴定具有变体的个体的“截止”值。结论：用特异性免疫分析系统测定血清LH， ...更多信息 MS可用于LHβ基因突变筛查，区分LHβ基因变异与正常。使用这些测定的KH值的比率来确定变体（<LH D2-LH D20.5）或野生型（>0.5）LH状态比率，该变体在妇科疾病患者中（18.4%）比在健康女性中（8.5%）更频繁地发生。排卵障碍患者中该变异的发生率（43.8%）高于其他患者（16.0%）。卵巢早衰、高催乳素血症和黄体功能不全在该变异患者中明显更常见。LH变异可能导致女性生殖障碍，包括不孕症和卵巢早衰。为了评估垂体刺激时变体LH的分泌比野生型LH更快，因为血清中变体LH显示出比野生型LH更快的增加，并达到更高的表观浓度，我们证实了突变型LHβ亚基纯合子受试者在GnRH刺激试验中显示出过度的LH反应，与PCOS患者的反应相似。然而，这种反应模式从变异LH没有表现出排卵障碍的关系。因此，变异型LH的生物学效应和临床意义需要进一步研究。少

项目成果

Kentaro Takahashi: "Increased prevalence of luteinizing hormone β-subunit variant in patients with premature ovarian failure" Fertility and Sterility. 71(1). 96-101 (1999)

Kentaro Takahashi：“卵巢早衰患者黄体生成素 β 亚基变异的患病率增加”，《生育与不育》71(1)。

Kentaro Takahashi: "Increased prevalence of luteinizing hormone β-subunit variant in Japanese infertility patients"Human Reproduction. 13 (12). 3338-3344 (1998)

Kentaro Takahashi：“日本不孕症患者黄体生成素 β 亚基变异的患病率增加”人类生殖 13 (12) 3338-3344 (1998)。

Kentaro Takahashi: "Increased prevalence of luteinizing hormone β-subunit variant in patients with premature ovarian failure"Fertility and Sterility. 71 (1). 96-101 (1998)

Kentaro Takahashi：“卵巢早衰患者黄体生成素 β 亚基变异的患病率增加”，《生育与不孕》71 (1)。

Hiroko Kurioka, Kentaro Takahashi, Maki Irikoma, Masako Okada, Tomoya Ozaki, Toshiko Ueda, Kohji Miyazaki: "Diagnostic difficulty in polycystic ovary syndrome due to an LH-β-subunit variant"European Journal of Endocrinology. 140. 235-238 (1999)

Hiroko Kurioka、Kentaro Takahashi、Maki Irikoma、Masako Okada、Tomoya Ozaki、Toshiko Ueda、Kohji Miyazaki：“LH-β-亚基变异导致多囊卵巢综合征的诊断困难”欧洲内分泌学杂志 140. 235-238 (1999) ）