Novel aspects of growth hormone (GH) autoregulation: GH-induced GH gene expression in grass carp pituitary cells through autocrine/paracrine mechanisms.
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.
Zhou
Hong
H
Kadoorie Biological Sciences Building, Department of Zoology, University of Hong Kong, Pokfulam Road, Hong Kong SAR, People's Republic of China.
Ko
Wendy K W
WK
Ho
Walter K K
WK
Stojilkovic
Stanko S
SS
Wong
Anderson O L
AO
D000818:Animals; D019898:Autocrine Communication / Q000502:physiology*; D002347:Carps / Q000502:physiology*; D015870:Gene Expression; D013006:Growth Hormone / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D006706:Homeostasis / Q000502:physiology*; D007106:Immune Sera / Q000494:pharmacology; D019899:Paracrine Communication / Q000502:physiology*; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D021541:Sea Bream; D015398:Signal Transduction; D013552:Swine
D007106:Immune Sera; D012333:RNA, Messenger; D013006:Growth Hormone