Hubei Province Engineering Laboratory for Pond Aquaculture, College of Fisheries, Huazhong Agricultural University, Wuhan, China.
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
Front Endocrinol (Lausanne). 2022 Oct 11;13:982297. doi: 10.3389/fendo.2022.982297. eCollection 2022.
Gonadotropin-releasing hormone (GnRH), as a vital hypothalamic neuropeptide, was a key regulator for pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the vertebrate. However, little is known about the other pituitary actions of GnRH in teleost. In the present study, two GnRH variants (namely, GnRH2 and GnRH3) and four GnRH receptors (namely, GnRHR1, GnRHR2, GnRHR3, and GnRHR4) had been isolated from grass carp. Tissue distribution displayed that GnRHR4 was more highly detected in the pituitary than the other three GnRHRs. Interestingly, ligand-receptor selectivity showed that GnRHR4 displayed a similar and high binding affinity for grass carp GnRH2 and GnRH3. Using primary culture grass carp pituitary cells as model, we found that both GnRH2 and GnRH3 could not only significantly induce pituitary reproductive hormone gene (GtHα, LHβ, FSHβ, INHBa, secretogranin-2) mRNA expression mediated by AC/PKA, PLC/IP/PKC, and Ca/CaM/CaMK-II pathways but also reduce dopamine receptor 2 (DRD2) mRNA expression the Ca/CaM/CaMK-II pathway. Interestingly, GnRH2 and GnRH3 could also stimulate anorexigenic peptide (POMCb, CART2, UTS1, NMBa, and NMBb) mRNA expression AC/PKA, PLC/IP/PKC, and Ca/CaM/CaMK-II pathways in grass carp pituitary cells. In addition, food intake could significantly induce brain GnRH2 mRNA expression. These results indicated that GnRH should be the coupling factor to integrate the feeding metabolism and reproduction in teleost.
促性腺激素释放激素(GnRH)作为一种重要的下丘脑神经肽,是脊椎动物垂体促黄体生成素(LH)和促卵泡激素(FSH)的关键调节因子。然而,关于 GnRH 在硬骨鱼中的其他垂体作用知之甚少。在本研究中,从草鱼中分离出两种 GnRH 变体(即 GnRH2 和 GnRH3)和四种 GnRH 受体(即 GnRHR1、GnRHR2、GnRHR3 和 GnRHR4)。组织分布显示,GnRHR4 在垂体中的检测水平高于其他三种 GnRHR。有趣的是,配体-受体选择性表明 GnRHR4 对草鱼 GnRH2 和 GnRH3 表现出相似的高结合亲和力。使用原代培养草鱼垂体细胞作为模型,我们发现 GnRH2 和 GnRH3 不仅可以通过 AC/PKA、PLC/IP/PKC 和 Ca/CaM/CaMK-II 途径显著诱导垂体生殖激素基因(GtHα、LHβ、FSHβ、INHBa、分泌颗粒素-2)mRNA 表达,还可以通过 Ca/CaM/CaMK-II 途径降低多巴胺受体 2(DRD2)mRNA 表达。有趣的是,GnRH2 和 GnRH3 还可以通过 AC/PKA、PLC/IP/PKC 和 Ca/CaM/CaMK-II 途径刺激草鱼垂体细胞中的厌食肽(POMCb、CART2、UTS1、NMBa 和 NMBb)mRNA 表达。此外,摄食可以显著诱导大脑 GnRH2 mRNA 表达。这些结果表明,GnRH 应该是整合硬骨鱼摄食代谢和生殖的偶联因子。