Novel aspects of growth hormone (GH) autoregulation: GH-induced GH gene expression in grass carp pituitary cells through autocrine/paracrine mechanisms

Endocrinology. 2004 Oct;145(10):4615-28. doi: 10.1210/en.2004-0163. Epub 2004 Jul 1.

Abstract

GH feedback on its own secretion at the pituitary level has been previously reported, but the mechanisms involved have not been elucidated. Here we examined the autocrine/paracrine effects of GH on GH synthesis using grass carp pituitary cells as a cell model. GH receptors were identified in carp somatotrophs, and their activation by exogenous GH increased steady-state GH mRNA levels and GH production. Removal of endogenous GH by immunoneutralization using GH antiserum inhibited basal as well as stimulated GH mRNA expression induced by GH-releasing factors in fish, including GnRH, apomorphine, and pituitary adenylate cyclase-activating polypeptide-38. Cytosolic mature GH mRNA levels were elevated by GH treatment and reduced by GH antiserum, whereas nuclear GH primary transcripts were almost undetectable after GH immunoneutralization. Inhibition of Janus kinase-2 (JAK2), phosphoinositide 3-kinase, and MAPK also abolished GH-induced steady-state GH mRNA expression. GH immunoneutralization in pituitary cells pretreated with actinomycin D induced a marked decrease in the half-life of GH mRNA, indicating that the clearance of GH transcripts could be enhanced by removing endogenous GH. These results provide evidence that GH can serve as a novel intrapituitary autocrine/paracrine factor maintaining GH gene expression in somatotrophs, and this action is mediated by JAK2/MAPK and JAK2/phosphoinositide 3-kinase cascades coupled to GH receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autocrine Communication / physiology*
  • Carps / physiology*
  • Gene Expression
  • Growth Hormone / genetics
  • Growth Hormone / immunology
  • Growth Hormone / metabolism*
  • Growth Hormone / pharmacology
  • Homeostasis / physiology*
  • Immune Sera / pharmacology
  • Paracrine Communication / physiology*
  • Pituitary Gland / cytology
  • Pituitary Gland / metabolism*
  • Pituitary Gland, Anterior / cytology
  • Pituitary Gland, Anterior / metabolism
  • RNA, Messenger / metabolism
  • Sea Bream
  • Signal Transduction
  • Swine

Substances

  • Immune Sera
  • RNA, Messenger
  • Growth Hormone