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Role of obestatin on growth hormone secretion: An in vitro approach
Authors:Yolanda Pazos  Carlos JP Álvarez  Jesús P Camiña  Omar Al-Massadi  Luísa M Seoane  Felipe F Casanueva
Institution:a Área de Endocrinología Molecular y Celular, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Santiago de Compostela, Spain
b CIBER Fisiopatología de la Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III, Spain
c Universidad de Santiago de Compostela (USC), Santiago de Compostela, Spain
Abstract:Obestatin, the ghrelin-associated peptide, showed to activate MAPK signaling with no effect on Akt nor cell proliferating activity in rat tumor somatotroph cells (growth cells, GC). A sequential analysis of the obestatin transmembrane signaling pathway indicated a route involving the consecutive activation of Gi, PI3k, novel PKCε, and Src for ERK1/2 activation. Furthermore, obestatin treatment triggers growth hormone (GH) release in the first 30 min, being more acute at 15 min. At 1 h, obestatin treated cells showed the same levels in GH secretion than controls. Added to this functionality, obestatin was secreted by GC cells. Based on the capacity to stimulate GH release from somatotroph cells, obestatin may act directly in the pituitary through an autocrine/paracrine mechanism.
Keywords:AC  adenylyl cyclase  ADP  adenosine diphosphate  cAMP  cyclic adenosine monophosphate  ChTX  cholera toxin  DAG  diacylglycerol  ERK  extracellular signal-regulated kinases  FBS  fetal bovine serum  GC  growth cells  GH  growth hormone  GHS-R1a  growth hormone secretagogue receptor type 1a  GPR-39  G protein coupled receptor 39  icv  intracerebroventricular  ip  intraperitoneal  iv  intravenous  MAPK  mitogen-activated protein kinases  PKC  protein kinase C  PI3k  phosphoinositide 3-kinase  PKA  cAMP-dependent protein kinase  PP2  4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3  4-d]pyrimidine  PP3  4-amino-7-phenylpyrazol[3  4-d]pyrimidine  PS  phosphatidyl serine  PTX  pertussis toxin  hRPE  human retinal pigment epithelium cells
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