Neuroendocrine regulation and transduction mechanisms in pituitary hormone release in fish

鱼类垂体激素释放的神经内分泌调节和转导机制

• 批准号: RGPIN-2015-05636
• 负责人: Chang, John
• 金额: $ 3.57万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=613660
• 关键词: Neuroendocrine; regulation; transduction; mechanisms; pituitary

Pituitary luteinizing hormone (LH) and growth hormone (GH) are important regulators of reproduction and growth in vertebrates. Multiple stimulatory and inhibitory brain hypothalamic neurohormones in turn control LH and GH secretion and production. Thus, studying the mechanisms by which the effects of these neurohormones are manifested at the level of the pituitary cells is important for understanding the physiological control of growth and reproduction. In goldfish, LH- and GH-cells share common, as well as distinct, regulators. For example, two gonadotropin-releasing hormones (GnRH2 and GnRH3), pituitary adenylate cyclase-activating polypeptide (PACAP) and ghrelin (gGRLN) stimulate both LH and GH secretion while dopamine (DA) inhibits LH, but stimulates GH, release. In contrast, GH-releasing hormone (gGHRH) stimulates GH, but attenuates LH, secretion. Understanding how the intracellular cellular changes (signal tranduction events) effected by these neurohormones interact to mediate their influences on LH and GH release and synthesis is integral to studying the physiological control of reproduction and growth. We have previously focused on how extracellular and intracellular Ca2+, protein kinase A (PKA), PKC, nitric oxide, extracellular-regulated kinase (ERK), phosphoinositide 3-kinase (PI3K) mediate the neuroendocrine control of LH and GH secretion and synthesis in goldfish pituitary cells. Using dispersed goldfish pituitary cells in primary culture, this grant proposal focuses on: 1) whether intracellular Ca2+ stores, PI3K and ERK mediate gGRLN actions on LH- and GH-cells, and how gGRLN receptor expression is affected by GnRH, DA, PACAP and gGHRH treatments; 2) the mechanisms mediating gGHRH stimulation of GH secretion and its novel inhibitory influence on LH release; 3) the transduction pathways mediating the LH and GH release responses to two goldfish kisspeptins, peptides that are thought to be involved in the regulation of puberty in vertebrates; 4) the mechanisms by which goldfish gonadotropin-inhibitory hormone exerts its seasonal-dependent inhibitory and stimulatory effects on hormone release and synthesis in LH- and GH-cells; 5) how PI3K interacts with other signal transduction components in mediating LH and GH release and synthesis, and in particular the differential actions of GnRH2 and GnRH3 on these processes; and 6) the differential expression and role of two known goldfish GnRH receptor isoforms on LH- and GH-cells. Results will contribute to our understanding of how neuroendocrine control of goldfish LH- and GH-cell functions are mediated and integrated, as well as the regulation control of growth and reproduction in goldfish and other teleosts, including important aquaculture species (such as cyprinids). Results will also be important for the basic understanding of ligand- and function-specific intracellular signaling in general.

黄体生成素（LH）和生长激素（GH）是脊椎动物生殖和生长的重要调节因子。多种刺激性和抑制性脑下丘脑神经激素反过来控制LH和GH的分泌和产生。因此，研究这些神经激素的作用在垂体细胞水平上表现出来的机制对于理解生长和生殖的生理控制是重要的。在金鱼中，LH-和GH-细胞共享共同的，以及不同的，监管机构。例如，两种促性腺激素释放激素（GnRH 2和GnRH 3），垂体腺苷酸环化酶激活多肽（PACAP）和生长素释放肽（gGRLN）刺激LH和GH分泌，而多巴胺（DA）抑制LH，但刺激GH释放。与此相反，生长激素释放激素（gGHRH）刺激生长激素，但减弱LH分泌。了解这些神经激素影响的细胞内细胞变化（信号转导事件）如何相互作用，以介导它们对LH和GH释放和合成的影响，是研究生殖和生长生理控制不可或缺的。我们以前集中在细胞外和细胞内Ca ~（2+），蛋白激酶A（PKA），蛋白激酶C（PKC），一氧化氮，细胞外调节激酶（ERK），磷酸肌醇3-激酶（PI 3 K）如何介导的LH和GH分泌和合成的神经内分泌控制在金鱼垂体细胞。 本研究以原代培养的金鱼脑垂体细胞为研究对象，探讨gGRLN对LH-和GH-细胞的作用、gGRLN受体的表达、gGHRH刺激GH分泌的机制以及gGHRH对LH分泌的抑制作用;（3）介导两种金鱼kisspeptins（被认为参与脊椎动物青春期调节的肽）的LH和GH释放反应的转导途径：（4）金鱼促性腺激素抑制激素对LH和GH细胞激素释放和合成的季节依赖性抑制和刺激作用的机制; 5）PI 3 K在介导LH和GH释放和合成中如何与其他信号转导组分相互作用，特别是GnRH 2和GnRH 3对这些过程的差异作用;和6）两种已知金鱼GnRH受体亚型在LH和GH细胞上的差异表达和作用。结果将有助于我们了解金鱼LH-和GH-细胞功能的神经内分泌控制是如何介导和整合的，以及金鱼和其他硬骨鱼，包括重要的水产养殖物种（如鲤）的生长和繁殖的调控。结果也将是重要的配体和功能特异性细胞内信号的基本理解一般。