Neuroendocrine regulation and transduction mechanisms in pituitary hormone release in fish

垂体前叶激素、生长激素（GH）和促性腺激素（GTH-II）是包括鱼类在内的脊椎动物生长和繁殖的重要调节因子。在硬骨鱼类中，直接支配垂体前叶的下丘脑神经元释放的大量刺激性和抑制性神经激素调节这些激素的分泌和产生。垂体细胞必须将这些刺激或抑制的细胞外信号转化为细胞内信号，然后调节激素的合成和释放。利用金鱼垂体细胞，我们研究了细胞内信号通路如何整合激素和功能特异性控制GH和GTH-II的分泌和合成。我们专注于两种内源性促性腺激素释放激素（GnRHs），多巴胺和PACAP的作用，特别是Ca2+，蛋白激酶A (PKA)， PKC和细胞外调节激酶（ERK）的作用。由不同的刺激因子产生的Ca2+信号具有独特的特征，并且可以由GH和GTH-II细胞中许多药理学上不同的细胞内Ca2+储存引起。虽然PKC和Ca2+对受刺激的激素分泌很重要，但ERK介导激素合成。即将到来的奖助金将解决以下问题。1)三种内源性金鱼脑生长抑素如何不同地抑制基础生长激素和诱导生长激素的释放和合成？2) ghrelin是最近发现的一种神经肽，已知在代谢和生长与生殖之间起桥梁作用，它如何刺激GTH-II和GH的释放，以及ghrelin是否调节其自身受体的表达？3)一氧化氮(NO)/cGMP信号是否参与gnrh诱导的GTH-II释放，NO与其他已知信号成分的关系如何？4)启动青春期的kisspeptin如何直接影响垂体激素的释放？5) pi -3激酶是否参与GH和GTH-II分泌的调节，而我们已经证明pi -3激酶可以影响gnrh诱导的GTH-II细胞中的Ca2+信号，这与其他已知的信号通路有何关系？这些拟议的研究将提供一个详细的检查在鱼类的生长和繁殖是如何调节在垂体细胞的水平。

Anterior pituitary hormones, growth hormone (GH) and gonadotropin (GTH-II), are important regulators of growth and reproduction in vertebrates, including fish. In bony fishes, numerous stimulatory and inhibitory neurohormones released from hypothalamic neurons directly innervating the anterior pituitary regulate the secretion and production of these hormones. A pituitary cell must translate these stimulatory or inhibitory extracellular signals to intracellular ones, which then regulate hormone synthesis and release. Using goldfish pituitary cells, we study how intracellular signaling pathways integrate the hormone- and function-specific control of GH and GTH-II secretion and synthesis. We have focused on the actions of two endogenous gonadotropin-releasing hormones (GnRHs), dopamine and PACAP, and especially the role of Ca2+, protein kinase A (PKA), PKC, and extracellular-regulated kinase (ERK). Ca2+ signals generated by different stimulatory factors have unique characteristics and can arise from a number of pharmacologically distinct intracellular Ca2+ stores in both GH and GTH-II cells. Although PKC and Ca2+ are important for stimulated hormone secretion, ERK mediates hormone synthesis. The upcoming grant will address the following questions. 1) How does three endogenous goldfish brain somatostatins differentially inhibit basal and induced GH release and synthesis? 2) How ghrelin, a recently discovered neuropeptide known to play a role in bridging metabolism and growth with reproduction, stimulates GTH-II and GH release, and does ghrelin regulate the expression of its own receptors? 3) Does nitric oxide (NO)/cGMP signaling participate in GnRH-induced GTH-II release and how is NO related to other known signaling components? 4) How does kisspeptin, which initiates puberty, directly affect pituitary hormone release? 5) Does PI-3-kinase, which we have shown to affect GnRH-induced Ca2+ signals in GTH-II cells, participate in the regulation of GH and GTH-II secretion, and how is this related to the other known signaling pathways? These proposed studies will provide a detailed examination of how growth and reproduction in fishes are regulated at the level of the pituitary cells.