Neuroendocrine regulation and transduction mechanisms in pituitary hormone release in fish

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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.**