Grewal N, Nagpal S, Chavali G B, Majumdar S S, Pal R, Salunke D M
National Institute of Immunology, New Delhi, India.
Biophys J. 1997 Sep;73(3):1190-7. doi: 10.1016/S0006-3495(97)78151-7.
A mechanism of signal transduction by human choriogonadotropin (hCG) has been proposed. Competitive inhibition of the binding of hCG to its receptor by the serine protease inhibitors led to the identification of local structural homology of an extracellular region of the receptor with the reactive site loop of chymotrypsin inhibitor. Synthetic peptides from the extracellular domain of luteinizing hormone-choriogonadotropin (LH/CG) receptor, rationally designed on the basis of this homology, were found to affect hormone-receptor binding and bioactivity. A receptor peptide incorporating one complete structural unit of the leucine-rich repeats motif of the extracellular domain of the receptor significantly increased hCG-receptor binding in a dose-dependent manner. However, the testosterone production in a Leydig cell bioassay was inhibited in the presence of this peptide. The agonistic effect on the hCG-receptor binding and the antagonistic effect on the testosterone production of a receptor peptide suggests the possibility of more than one quasi-equivalent receptor-binding site on the hormone. Hormone-induced receptor oligomerization may therefore be involved in the mechanism of signal transduction by hCG.
已经提出了人绒毛膜促性腺激素（hCG）的信号转导机制。丝氨酸蛋白酶抑制剂对hCG与其受体结合的竞争性抑制作用，导致鉴定出受体细胞外区域与胰凝乳蛋白酶抑制剂反应位点环的局部结构同源性。基于这种同源性合理设计的来自促黄体生成素-绒毛膜促性腺激素（LH/CG）受体细胞外结构域的合成肽，被发现会影响激素-受体结合和生物活性。一种包含受体细胞外结构域富含亮氨酸重复基序一个完整结构单元的受体肽，以剂量依赖方式显著增加了hCG-受体结合。然而，在该肽存在的情况下，睾丸间质细胞生物测定中的睾酮产生受到抑制。受体肽对hCG-受体结合的激动作用和对睾酮产生的拮抗作用表明，激素上可能存在不止一个准等效受体结合位点。因此，激素诱导的受体寡聚化可能参与hCG的信号转导机制。
