Identification and structural characterization of the neuronal luteinizing hormone receptor associated with sensory systems
Identification and structural characterization of the neuronal luteinizing hormone receptor associated with sensory systems
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DOI：
10.1074/jbc.m311395200
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发表时间：
2004-01-16
影响因子：
4.8
通讯作者：
Rajaniemi, HJ
中科院分区：
文献类型：
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作者：
Apaja, PM;Harju, KT;Rajaniemi, HJ
黄体生成素受体(LHR)是一种G蛋白偶联受体，参与卵巢和睾丸功能的调节。在这里，我们表明，受体也存在于外周和中枢神经系统的特定区域，因此可能具有比预期更广泛的功能作用。成年和发育中的大鼠神经组织从胚胎14.5天开始表达全长LHR mRNA和两种受体蛋白M-r 90,000和73,000，分别代表成熟和前体形式。该受体经配基亲和层析纯化后具有与配体结合的能力，人绒毛膜促性腺激素和黄体生成素能够以剂量依赖的方式取代I-125标记的人绒毛膜促性腺激素与胎头膜的结合。最后，两个大鼠LHR基因的5‘侧翼序列(类似于2和4kb)被证明将LacZ报告基因的表达定向到胎儿和成年转基因小鼠的外周和中枢神经系统的特定区域，特别是与感觉、记忆、生殖行为和自主神经功能相关的结构。重要的是，转基因活性仅限于神经元，并与细胞色素P450侧链裂解酶共定位。综上所述，这些结果表明神经元LHR是一种功能蛋白，可能通过调节神经类固醇的合成在神经元的发育和功能中发挥作用。
The luteinizing hormone receptor (LHR) is a G protein-coupled receptor involved in regulation of ovarian and testicular functions. Here we show that the receptor is present also in specific areas of the peripheral and central nervous system and may thus have a broader functional role than has been anticipated. Full-length LHR mRNA and two receptor protein species of M-r 90,000 and 73,000, representing mature and precursor forms, respectively, were expressed in adult and developing rat nervous tissue, starting at fetal day 14.5. The receptor was capable of ligand binding because it was purified by ligand affinity chromatography, and human chorionic gonadotropin and LH were able to displace I-125-labeled human chorionic gonadotropin binding to fetal head membranes in a dose-dependent manner. Finally, two 5'-flanking sequences (similar to2 and 4 kb) of the rat LHR gene were shown to direct expression of the lacZ reporter to specific areas of the peripheral and central nervous system in fetal and adult transgenic mice, especially to structures associated with sensory, memory, reproductive behavior, and autonomic functions. Importantly, the transgene activity was confined to neurons and colocalized with the cytochrome P450 side chain cleavage enzyme. Taken together, these results indicate that the neuronal LHR is a functional protein, implicating a role in neuronal development and function, possibly by means of regulating synthesis of neurosteroids.