title: MEK1/2 differentially participates in GnRH actions on goldfish LH and GH secretion and hormone protein availability: acute and long-term effects, in vitro.
abstract: Two endogenous gonadotropin-releasing hormones (GnRHs), sGnRH and cGnRH-II, stimulate LH and GH release via protein kinase C (PKC) signaling in goldfish. In this study, extracellular signal-regulated kinase kinase 1 and 2 (MEK1/2) involvement in acute and prolonged GnRH effects on goldfish gonadotrope and somatotrope functions, as well as potential interactions with PKC in the control of LH and GH release from goldfish pituitary cells was investigated. MEK1/2 inhibitors U0126 and PD098059 significantly decreased sGnRH but not cGnRH-II-stimulated GH release from perifused goldfish pituitary cells and U0126 significantly reduced the GH, but not the LH, release responses to synthetic PKC activators. In long-term static incubations (up to 24h) with goldfish pituitary cells, U0126 generally did not affect basal LH release but attenuated sGnRH- and cGnRH-II-induced LH release, as well as the time-dependent effects of sGnRH and/or cGnRH-II to elevate total LH availability (sum of release and cell content). sGnRH and cGnRH-II reduced cellular GH content and/or total GH availability at 2, 6, and 12h while static incubation with U0126 alone generally increased basal GH release but reduced cellular GH content and/or the total amount of GH available. U0126 also selectively reduced the sGnRH-induced GH release responses at 6 and 24h but paradoxically inhibited cGnRH-II-stimulated GH secretion while enhancing sGnRH-elicited GH release at 2h. Taken together, this study reveals the complexity of GnRH-stimulated MEK1/2 signaling and adds to our understanding of cell-type- and GnRH-isoform-selective signal transduction in the regulation of pituitary cell hormone release and production.
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Joshua G
authors.initials: JG
authors.lastname: Pemberton
authors.forename: Michael E
authors.initials: ME
authors.lastname: Orr
authors.forename: Morgan
authors.initials: M
authors.lastname: Booth
authors.forename: John P
authors.initials: JP
authors.lastname: Chang
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006054:Goldfish / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000235:genetics / Q000378:metabolism*; D048369:MAP Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048370:MAP Kinase Kinase 2 / Q000235:genetics / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002070:Butadienes; D005419:Flavonoids; D009570:Nitriles; C113580:U 0126; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D013006:Growth Hormone; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: MEK1/2 and ERK1/2 signaling; PKC signaling; Perifusion and static incubation; Primary cultures of dispersed goldfish pituitary cells; U0126 and PD098059