title: Differential involvement of protein kinase C and protein kinase A in ghrelin-induced growth hormone and gonadotrophin release from goldfish (Carassius auratus) pituitary cells.
abstract: Ghrelin (GRLN) and its receptor have been identified and characterised in goldfish brain and the pituitary, and recent evidence shows that goldfish (g)GRLN(19)  induces both growth hormone (GH) and maturational gonadotrophin (LH) release through an extracellular Ca(2+) -dependent mechanism in goldfish. To further understand the role of GRLN in hormone release, the present study examined the involvement of protein kinase C (PKC) and protein kinase A (PKA) in gGRLN(19) -induced GH and LH release and corresponding Ca(2+)  signals in primary cultures of goldfish pituitary cells. Treatments with PKC inhibitors, Bis-II and Gö 6976, significantly reduced gGRLN(19) -induced GH and LH release and their corresponding intracellular Ca(2+)  signals in identified somatotrophs and gonadotrophs, respectively. gGRLN(19)  was unable to further stimulate hormone release or Ca(2+)  signals when cells were pretreated with the PKC agonist, DiC8. PKA inhibitors, H-89 and KT 5720, inhibited gGRLN(19) -induced LH release and Ca(2+)  signals in gonadotrophs but not GH release or Ca(2+)  signals in somatotrophs. Interestingly, pretreatment of pituitary cells with the adenylate cyclase activator forskolin potentiated gGRLN(19) -induced GH, but not LH, release, although it had no effect on intracellular Ca(2+)  signals in either cell type. Taken together, the results suggest that PKC is an important intracellular component in gGRLN(19) -induced GH and LH release, whereas PKA is involved in gGRLN(19) -elicited LH release. Furthermore, the PKA pathway potentiates gGRLN(19) -induced GH release via a Ca(2+) -independent mechanism. Overall, the present study provides insight into the neuroendocrine regulation of GH and LH release by elucidating the mechanistic aspects of GRLN, a hormone involved in many critical physiological processes, including pituitary functions.
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: C L
authors.initials: CL
authors.lastname: Grey
authors.forename: J P
authors.initials: JP
authors.lastname: Chang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D004075:Diglycerides / Q000494:pharmacology; D005260:Female; D054439:Ghrelin / Q000737:chemistry / Q000494:pharmacology*; D006054:Goldfish; D006062:Gonadotropins / Q000378:metabolism*; D013006:Growth Hormone / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D002227:Carbazoles; D004075:Diglycerides; D054439:Ghrelin; D006062:Gonadotropins; D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; C044295:1,2-dioctanoylglycerol; C081021:Go 6976; D013006:Growth Hormone; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D002118:Calcium