Kim Hyeon Soo, Yumkham Sanatombi, Choi Jang Hyun, Son Gi Hoon, Kim Kyungjin, Ryu Sung Ho, Suh Pann-Ghill
Division of Molecular and Life Science, Department of Life Science, Pohang University of Science and Technology, San31 Hyoja-Dong Nam-Gu Pohang, Kyungbuk 790-784, South Korea.
J Endocrinol. 2006 Sep;190(3):581-91. doi: 10.1677/joe.1.06727.
Serotonin is a neurotransmitter that alters the hypothalamic-pituitary-adrenal axis. To date, however, the molecular mechanisms underlying the role of serotonin in hormone secretion have remained largely unclear. In this study, we report that serotonin activates phospholipase C (PLC) gamma1 in an Src-dependent manner in hypothalamic GT1-7 cells, and that pretreatment with either 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazole [3, 4-d] pyrimidine, an Src-kinase inhibitor, or U73122, a PLC inhibitor, attenuates the serotonin-induced increase in calcium levels. Also, PLC gamma1 binds to c-Src through the Src-homology (SH) 223 domain upon serotonin treatment. Moreover, calcium increase is alleviated in the cells transientlyexpressing SH223 domain-deleted PLC gamma1 or lipase inactive mutant PLC gamma1, as compared with cells transfected with wild-type PLC gamma1. Furthermore, the inhibition of the activities of either PLC or Src results in a significant diminution of the serotonin-induced release of gonadotropin-releasing hormone (GnRH). In addition, the results of our small-interfering RNA experiment confirm that endogenous PLC gamma1 is a prerequisite for serotonin-mediated signaling pathways. Taken together, our findings demonstrate that serotonin stimulates the release of GnRH through the Src-PLC gamma1 pathway, via the modulation of intracellular calcium levels.
血清素是一种可改变下丘脑 - 垂体 - 肾上腺轴的神经递质。然而，迄今为止，血清素在激素分泌中作用的分子机制仍基本不清楚。在本研究中，我们报告血清素在下丘脑GT1 - 7细胞中以Src依赖的方式激活磷脂酶C（PLC）γ1，并且用Src激酶抑制剂4 - 氨基 - 5 -（4 - 氯苯基）- 7 -（叔丁基）吡唑[3,4 - d]嘧啶或PLC抑制剂U73122预处理可减弱血清素诱导的钙水平升高。此外，血清素处理后，PLCγ1通过Src同源（SH）223结构域与c - Src结合。而且，与转染野生型PLCγ1的细胞相比，瞬时表达缺失SH223结构域的PLCγ1或脂肪酶无活性突变体PLCγ1的细胞中钙升高得到缓解。此外，抑制PLC或Src的活性会导致血清素诱导的促性腺激素释放激素（GnRH）释放显著减少。另外，我们的小干扰RNA实验结果证实内源性PLCγ1是血清素介导的信号通路的先决条件。综上所述，我们的研究结果表明血清素通过Src - PLCγ1途径，通过调节细胞内钙水平来刺激GnRH的释放。
