Tsutsumi M, Zhou W, Millar R P, Mellon P L, Roberts J L, Flanagan C A, Dong K, Gillo B, Sealfon S C
Fishberg Research Center in Neurobiology, Mount Sinai School of Medicine, New York, New York 10029.
Mol Endocrinol. 1992 Jul;6(7):1163-9. doi: 10.1210/mend.6.7.1324422.
GnRH plays a pivotal role in the reproductive system, and GnRH analogs have wide therapeutic applications ranging from the treatment of prostatic cancer to infertility. Determination of the predicted structure of the GnRH receptor (GnRHR) would illuminate the mechanisms of receptor activation and regulation and allow directed design of improved GnRH analogs. We report the cloning of a cDNA representing the mouse GnRHR and confirm its identity using Xenopus oocyte expression. Injection of sense RNA transcript leads to the expression of a functional, high affinity GnRHR. Expression of the GnRHR using gonadotrope cell line RNA, however, is blocked by an antisense oligonucleotide. In situ hybridization in the rat anterior pituitary reveals a characteristic GnRHR distribution. The nucleotide sequence encodes a 327-amino acid protein which has the seven putative transmembrane domains characteristic of G protein-coupled receptors, but which lacks a typical intracellular C-terminus. The unusual structure and novel potential regulatory domain of the GnRHR may explain unique aspects of its signal transduction and regulation.
促性腺激素释放激素（GnRH）在生殖系统中起关键作用，GnRH类似物具有广泛的治疗应用，从前列腺癌的治疗到不孕症的治疗。确定GnRH受体（GnRHR）的预测结构将阐明受体激活和调节的机制，并有助于定向设计改良的GnRH类似物。我们报告了代表小鼠GnRHR的cDNA的克隆，并使用非洲爪蟾卵母细胞表达证实了其身份。注射正义RNA转录本可导致功能性高亲和力GnRHR的表达。然而，使用促性腺激素细胞系RNA表达GnRHR会被反义寡核苷酸阻断。大鼠垂体前叶的原位杂交显示出GnRHR的特征性分布。核苷酸序列编码一种327个氨基酸的蛋白质，该蛋白质具有G蛋白偶联受体特有的七个推定跨膜结构域，但缺乏典型的细胞内C末端。GnRHR的异常结构和新的潜在调节结构域可能解释了其信号转导和调节的独特方面。
