Novel Aspects of Growth Hormone (GH) Autoregulation: GH-Induced GH Gene Expression in Grass Carp Pituitary Cells through Autocrine/Paracrine Mechanisms

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.

Leptin activates chicken growth hormone promoter without chicken STAT3 in vitro

“…suggests that GH upregulates GH mRNA expression through the MAPK and PI3K pathways in somatotrophs of the grass carp (Zhou et al, 2004). Furthermore, inhibition of p42/44 MAPK, p38 MAPK, and PI3K signaling blocks interleukin 1β-stimulated GH mRNA expression in GH3 cells (Gong et al, 2005).…”

Grass carp prolactin: Molecular cloning, tissue expression, intrapituitary autoregulation by prolactin and paracrine regulation by growth hormone and luteinizing hormone

“…In our previous studies, intrapituitary autoregulation of GH (Zhou et al, 2004a) and somatolactin (Jiang and Wong, 2013) via autocrine/paracrine mechanisms has been reported in grass carp pituitary cells. In the same animal model, an "intrapituitary feedback loop" for GH regulation has also been documented (Wong et al, 2006).…”

Signaling mechanisms for α2-adrenergic inhibition of PACAP-induced growth hormone secretion and gene expression grass carp pituitary cells

“…After that, total RNA was digested with DNase I (Pharmacia) to remove potential contamination of genomic DNA and reverse transcribed with SuperScript II (Invitrogen) using oligo(dT18) as the primer. The RT samples obtained were then subjected to quantitative PCR for GH primary transcript using a Rotor Gene 2000 real-time amplification system (Corbett Research, Mortlake, NSW, Australia) as described previously (64). Expression of mature GH mRNA was also assayed in these samples by using a similar approach to serve as a parallel control.…”