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This version published online on July 1, 2004
Endocrinology, doi:10.1210/en.2004-0163
A more recent version of this article appeared on October 1, 2004
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Submitted on February 9, 2004
Accepted on June 28, 2004

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

Hong Zhou, Wendy K. W. Ko, Walter K. K. Ho, Stanko S. Stojilkovic, and Anderson O. L. Wong*

Department of Zoology, University of Hong Kong, Pokfulam Road, Hong Kong; Department of Biochemistry, Chinese University of Hong Kong, Shatin, N.T., Hong Kong; Endocrinology & Reproduction Research Branch, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892-4510, USA

* To whom correspondence should be addressed. E-mail: olwong{at}hkucc.hku.hk.

Growth hormone (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 PACAP. 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 JAK2, PI3K, 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/PI3K cascades coupled to GH receptors.
Key words: Growth hormone • autocrine/paracrine actions • GH mRNA stability • GH primary transcript • real-time PCR • laser capture microdissection • pituitary cells • grass carp




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