Neuroendocrine regulation and transduction mechanisms in pituitary hormone release in fish

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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.