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。在硬骨鱼中，下丘脑神经元释放的大量刺激性和抑制性神经激素直接支配垂体前叶，调节这些激素的分泌和产生。脑垂体细胞必须将这些细胞外的刺激性或抑制性信号转化为细胞内的信号，然后细胞内的信号调节激素的合成和释放。利用金鱼脑垂体细胞，我们研究了细胞内信号通路如何整合激素和功能特异性的GH和GTH-II分泌和合成的控制。我们着重于两种内源性促性腺激素释放激素(GnRHs)的作用，即多巴胺和PACAP，特别是钙离子、蛋白激酶A(PKA)、蛋白激酶C(PKC)和细胞外调节激酶(ERK)的作用。由不同刺激因子产生的钙信号具有独特的特征，可以来自GH和GTH-II细胞中许多药理上不同的细胞内钙储存。虽然PKC和Ca~(2+)对刺激的激素分泌很重要，但ERK介导激素的合成。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如何不同地抑制基础和诱导的GH释放和合成？2)最近发现的一种神经肽Ghrelin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的释放以及NO与其他已知信号成分的关系？4)启动青春期的Kispeptin如何直接影响脑下垂体激素的释放？5)PI-3-K，我们已经证明它们影响GnRH诱导的GTH-II细胞中的钙信号，参与GH和GTH-II分泌的调节，这与其他已知的信号通路有何关系？这些拟议的研究将详细检查鱼类的生长和繁殖是如何在脑垂体细胞水平上进行调节的。

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.