Clinical application and study for signal transduction of human LH-receptor

人LH受体信号转导的临床应用及研究

• 批准号: 14571540
• 负责人: SHINOZAKI Hiromitsu
• 金额: $ 2.24万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571540/
• 关键词: LH receptor; gonadotropin receptor; GPCRs; constitutively active mutant; cAMP; phosphodiesterase; precocious puberty; ヒトLHレセプター; 点突然変異; TGF-β

The human LH receptor belongs to the family of G protein-coupled receptor. The LH receptor is expressed in the gonad, where it plays a pivotal role in both male and female reproductive physiology. On a cellular level, the binding of LH to the LH-R on gonadal target cells causes the stimulation of Gs, which in turn activates adenylyl cyclase, resulting in increased intracellular concentrations of cAMP.In our recent experiment, the LH-R (L457R) mutant was both constitutively active and unresponsive to further hormonal stimulation as determined on both intact cells and isolated membranes. When coexpressed at submaximal concentrations, L457R does not decrease the cell surface expression of LH-R. Coexpression of L457R, however, causes an attenuation of LH-stimulated cAMP production by LH-R. We found that this attenuation was caused by an activation of the phosphodiesterase (PDE) 4D3.

人LH受体属于G蛋白偶联受体家族。LH受体在性腺中表达，在男性和女性生殖生理学中起关键作用。在细胞水平上，LH与性腺靶细胞上的LH-R的结合引起Gs的刺激，Gs又激活腺苷酸环化酶，导致细胞内cAMP浓度增加。在我们最近的实验中，LH-R（L457 R）突变体在完整细胞和分离的膜上都具有组成性活性，并且对进一步的激素刺激无反应。当以次最大浓度共表达时，L457 R不降低细胞表面LH-R的表达。然而，L457 R的共表达导致LH刺激的cAMP产生由LH-R减弱。我们发现，这种衰减是由磷酸二酯酶（PDE）4D 3的激活引起的。

项目成果

Kyoko Inoue: "Mechanisms of Action of Transforming Growth Factor-{beta} on the Expression of Follicle-Stimulating Hormone Receptor Messenger Ribonucleic Acid Levels in Rat Granulosa Cells."Biology of Reproduction. 69・4. 1238-1244 (2003)

Kyoko Inoue：“转化生长因子-{β}对大鼠颗粒细胞中卵泡刺激激素受体信使核糖核酸水平的作用机制”，《生殖生物学》69·4。

Megumi Tsuchiya: "Expression of steroidogenic acute regulatory protein (StAR) and LH receptor in MA-10 cells."Life Sciences. 73・22. 2855-2863 (2003)

Megumi Tsuchiya：“MA-10 细胞中类固醇生成急性调节蛋白 (StAR) 和 LH 受体的表达。”生命科学 73・22 2855-2863 (2003)。

Takashi Minegishi: "The Ovary Second Edition"Elsevier Academic Press. 664 (2004)

峰岸隆：《卵巢第二版》爱思唯尔学术出版社。

Hiromitsu Shinozaki: "Desensitization of Gs-coupled Receptor Signaling by Constitutively Active Mutants of the Human Lutrpin/Choriogonadtropin Receptor"The Journal of Clinical Endocrinology & Metabolism. 88・3. 1194-1204 (2003)

Hiromitsu Shinozaki：“人 Lutrpin/绒毛膜促性腺激素受体的组成型活性突变体对 Gs 偶联受体信号的脱敏”《临床内分泌与代谢杂志》88・3。

篠崎博光: "FSH受容体の分子生物学的研究の現状"産婦人科の世界. 55・春期増刊号. 4-9 (2003)

筱崎弘光：“FSH 受体分子生物学研究现状”《妇产科世界》55 春季特刊（2003 年）。