Differential modulation of ghrelin-induced GH and LH release by PACAP and dopamine in goldfish pituitary cells
2013
Grey, Caleb L. | Chang, John P.
Ghrelin (GRLN) participates in multiple physiological processes, including the regulation of growth hormone (GH) and luteinizing hormone (LH) release. In the goldfish, neuroendocrine control of GH and LH release are multifactorial. In this system, pituitary adenylate cyclase-activating polypeptide (PACAP)-stimulated GH and LH secretion, as well as dopamine (DA)-induced GH release, are mediated by protein kinase A (PKA)-dependent, but protein kinase C (PKC)-independent, mechanisms. In addition, DA inhibits LH secretion by actions at sites along both PKA and PKC signaling pathways. Recently, goldfish GRLN (gGRLN₁₉) has been shown to induce GH release via PKC, and LH secretion via both PKC and PKA. To further understand the neuroendocrine regulation of goldfish GH and LH release, we examined the effects of DA and PACAP on gGRLN₁₉ actions in primary cultures of goldfish pituitary cells in perifusion and in Ca²⁺-imaging experiments. Consistent with their known intracellular signaling mechanisms in gonadotrophs, DA inhibited gGRLN₁₉-induced LH release while cotreatment of PACAP and gGRLN₁₉ did not produce additive LH responses. When applied prior to gGRLN₁₉, PACAP potentiated gGRLN₁₉-induced GH release and Ca²⁺ signals within somatotrophs. In contrast, neither prior treatment with DA followed by gGRLN₁₉ nor pretreatment with gGRLN₁₉ prior to PACAP produced an enhanced GH release response. These observations suggest that PKA activators positively modulate gGRLN₁₉ actions on goldfish somatotrophs in a ligand- and treatment order-specific manner. Results add to our understanding of the complexity of neuroendocrine control of GH and LH release at the pituitary cell level, and our understanding of GRLN action.
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