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Am J Physiol Endocrinol Metab 292: E1750-E1762, 2007. First published February 20, 2007; doi:10.1152/ajpendo.00001.2007
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Signaling mechanisms for {alpha}2-adrenergic inhibition of PACAP-induced growth hormone secretion and gene expression grass carp pituitary cells

Xinyan Wang, Mable M. S. Chu, and Anderson O. L. Wong

Department of Zoology, University of Hong Kong, Hong Kong, China

Submitted 2 January 2007 ; accepted in final form 2 February 2007

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent growth hormone (GH)-releasing factor in lower vertebrates. However, its functional interactions with other GH regulators have not been fully characterized. In fish models, norepinephrine (NE) inhibits GH release at the pituitary cell level, but its effects on GH synthesis have yet to be determined. We examined adrenergic inhibition of PACAP-induced GH secretion and GH gene expression using grass carp pituitary cells as a cell model. Through activation of pituitary {alpha}2-adrenoreceptors, NE or the {alpha}2-agonist clonidine reduced both basal and PACAP-induced GH release and GH mRNA expression. In carp pituitary cells, clonidine also suppressed cAMP production and intracellular Ca2+ levels and blocked PACAP induction of these two second messenger signals. In GH3 cells transfected with a reporter carrying the grass carp GH promoter, PACAP stimulation increased GH promoter activity, and this stimulatory effect could be abolished by NE treatment. In parallel experiments, clonidine reduced GH primary transcript and GH promoter activity without affecting GH mRNA stability, and these inhibitory actions were mimicked by inhibiting adenylate cyclase (AC), blocking protein kinase A (PKA), removing extracellular Ca2+ in the culture medium, or inactivating L-type voltage-sensitive Ca2+ channels (VSCC). Since our recent studies have shown that PACAP can induce GH secretion in carp pituitary cells through cAMP/PKA- and Ca2+/calmodulin-dependent mechanisms, these results, taken together, suggest that {alpha}2-adrenergic stimulation in the carp pituitary may inhibit PACAP-induced GH release and GH gene transcription by blocking the AC/cAMP/PKA pathway and Ca2+ entry through L-type VSCC.

pituitary adenylate cyclase-activating polypeptide; growth hormone; signal transduction; norepinephrine



Address for reprint requests and other correspondence: A. O. L. Wong, Dept. of Zoology, Univ. of Hong Kong, Pokfulam Road, Hong Kong, China (e-mail: olwong{at}hkucc.hku.hk)




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Q. Jiang, M. He, X. Wang, and A. O. L. Wong
Grass carp somatolactin: II. Pharmacological study on postreceptor signaling mechanisms for PACAP-induced somatolactin-{alpha} and -{beta} gene expression
Am J Physiol Endocrinol Metab, August 1, 2008; 295(2): E477 - E490.
[Abstract] [Full Text] [PDF]




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