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），是脊椎动物（包括鱼类）生长和繁殖的重要调节因子。 在硬骨鱼中，直接支配垂体前叶的下丘脑神经元释放的许多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性或抑制性的细胞外信号翻译成细胞内信号，然后细胞内信号调节激素的合成和释放。使用金鱼垂体细胞，我们研究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。我们已经集中在两个内源性促性腺激素释放激素（GnRHs），多巴胺和PACAP的行动，特别是Ca 2+，蛋白激酶A（PKA），蛋白激酶C和细胞外调节激酶（ERK）的作用。由不同的刺激因子产生的Ca 2+信号具有独特的特征，并且可以由GH和GTH-II细胞中许多不同的细胞内Ca 2+储存产生。虽然PKC和Ca 2+对刺激激素分泌很重要，但ERK介导激素合成。即将到来的赠款将解决以下问题。1)三种内源性金鱼脑生长抑素是如何不同地抑制基础和诱导生长激素的释放和合成的？ 2)Ghrelin是最近发现的一种神经肽，已知在代谢和生长与生殖的桥梁中发挥作用，它如何刺激GTH-II和GH的释放，Ghrelin是否调节其自身受体的表达？3)一氧化氮（NO）/cGMP信号通路是否参与GnRH诱导的GTH-Ⅱ释放？NO与其他已知的信号通路成分有何关系？ 4)启动青春期的kisspeptin如何直接影响脑垂体激素的释放？ 5)PI-3-激酶，我们已经证明，影响GnRH诱导的Ca 2+信号在GTH-II细胞，参与GH和GTH-II分泌的调节，这是如何与其他已知的信号通路？这些拟议中的研究将提供一个详细的检查如何在垂体细胞的水平上调节鱼类的生长和繁殖。

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.