Human peripheral blood mononuclear cells express gonadotropin-releasing hormone (GnRH), GnRH receptor, and interleukin-2 receptor γ-chain messenger ribonucleic acids that are regulated by GnRH in vitro
Human peripheral blood mononuclear cells express gonadotropin-releasing hormone (GnRH), GnRH receptor, and interleukin-2 receptor γ-chain messenger ribonucleic acids that are regulated by GnRH in vitro
复制标题
DOI：
10.1210/jc.84.2.743
复制
发表时间：
1999-02-01
影响因子：
5.8
通讯作者：
Leung, PCK
中科院分区：
文献类型：
--
作者：
Chen, HF;Jeung, EB;Leung, PCK
下丘脑十肽GnRH在人类生殖中起着关键作用。除了已知GnRH对垂体细胞的作用外，有证据支持在垂体细胞以外的组织（包括淋巴细胞）中存在GnRH结合位点。此外，已发现GnRH样物质从淋巴细胞分泌。然而，GnRH分泌和结合在免疫细胞中的确切性质尚未完全确定。本研究采用RT-PCR方法检测了人外周血单个核细胞中GnRH、GnRH受体（GnRHR）和白细胞介素-α受体γ链信使核糖核酸（mRNA）的表达和调控。结果发现，人单个核细胞表达GnRH和GnRHR mRNA。这些mRNA的核苷酸序列分别与它们的下丘脑和垂体对应物相同。此外，GnRH及其合成类似物在体外调节外周血单个核细胞中GnRH和GnRHR mRNA的表达。不同浓度的GnRH（10（-5）~ 10（-11）mol/L）处理可剂量依赖性地增加GnRHRmRNA的表达（10（-8）mol/LGnRH时最高为对照组的158%，P < 0.05），但10（-9）mol/LGnRH使GnRHRmRNA的表达降低至对照组的69%（P < 0.05）。GnRH拮抗剂的GnRH的共治疗阻断了这些调节作用，表明受体介导的性质的GnRH的行动。GnRH和GnRH激动剂均以剂量依赖性方式刺激IL-2受体γ链mRNA，表明GnRH可能参与淋巴细胞活化。总之，这些观察结果表明，编码垂体型GnRH HR和下丘脑型GnRH的mRNA也在人外周血单核细胞中表达。淋巴细胞内源性分泌GnRH可能作为一种自分泌或旁分泌因子调节免疫功能。由于淋巴细胞上存在GnRH受体，外源性GnRH类似物治疗可能通过这些受体对免疫系统产生影响。
The hypothalamic decapeptide, GnRH, plays a critical role in human reproduction. In addition to the well known effects of GnRH on pituitary cells, there is evidence supporting the presence of GnRH-binding sites in tissues other than pituitary cells, including lymphocytes. In addition, a GnRH-like substance has been found to be secreted from lymphoid cells. However, the precise nature of GnRH secretion and binding in immune cells has not been fully established. In this study, we used the RT-PCR method to examine the expression and regulation of GnRH, GnRH receptor (GnRHR), and interleukin-a receptor gamma-chain messenger ribonucleic acids (mRNAs) in human peripheral blood mononuclear cells. It was found that human mononuclear cells expressed GnRH and GnRHR mRNAs. Nucleotide sequences of these mRNAs are identical to their hypothalamic and pituitary counterparts, respectively. In addition, GnRH and GnRHR mRNA expressions in peripheral blood mononuclear cells are regulated by GnRH and its synthetic analogs in vitro. Treatment with various concentrations of GnRH (10(-5)-10(-11) mol/L) increased GnRHR mRNA expression in a dose-dependent manner (maximal level is 158% of the untreated control value at 10(-8) mol/L GnRH; P < 0.05), but reduced GnRH mRNA levels to 69% of the untreated control value at 10(-9) mol/L GnRH (P < 0.05). Cotreatment of GnRH with a GnRH antagonist blocked these regulatory effects, indicating the receptor-mediated nature of the GnRH action. Both GnRH and GnRH agonist stimulated interleukin-2 receptor gamma-chain mRNA in a dose-dependent manner, indicating that GnRH may be involved in lymphocyte activation. In summary, these observations suggest that mRNAs encoding the pituitary form of GnRHR and the hypothalamic form of GnRH are also expressed in human peripheral blood mononuclear cells. The endogenous production of GnRH by lymphocytes may act as an autocrine or paracrine factor to regulate immune functions. Because of the presence of GnRHR on lymphocytes, exogenous GnRH analog therapy may have an impact on the immune system through these receptors.