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This Article Full Text Full Text (PDF) All Versions of this Article: 292/6/E1899    most recent 00116.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Iwasaki, Y. Articles by Hashimoto, K. Search for Related Content PubMed PubMed Citation Articles by Iwasaki, Y. Articles by Hashimoto, K.

Activation of AMP-activated protein kinase stimulates proopiomelanocortin gene transcription in AtT20 corticotroph cells

¹Department of Endocrinology, Metabolism, and Nephrology, Kochi Medical School, Kochi University, Nankoku; and Departments of ²Medicine and ³Clinical Pathophysiology, Nagoya University Graduate School of Medicine and Hospital, Nagoya, Japan

Submitted 12 March 2006 ; accepted in final form 21 February 2007

Starvation is known to activate the hypothalamo-pituitary-adrenal (HPA) axis, a representative antistress system in the living organism. In this study, we investigated in vitro whether activation of the AMP-activated protein kinase (AMPK), which is known to occur in intracellular energy depletion, influences the expression of POMC gene that encodes adrenocorticotropin. We first confirmed that each subunit of AMPK was expressed in the AtT20 corticotroph cell line. We then found that AICAR, a cell-permeable AMP analog and an activator of AMPK, potently stimulated the 5'-promoter activity of POMC gene in a dose-dependent manner. The effects were promoter specific because AICAR enhanced the AP1-mediated POMC promoter activities but did not influence other transcription factor-induced transcription. The effect of AICAR on POMC gene transcription was completely eliminated by specific AMPK inhibitor compound C or by dominant negative AMPK, whereas overexpression of constitutively active AMPK mimicked the effect of AICAR. Finally, experiments using specific kinase inhibitors suggested that the PI 3-kinase-mediated signaling pathway is at least partly involved in the effect. Our results suggest that intracellular energy depletion with the resultant activation of AMPK directly stimulates the HPA axis at the pituitary level by increasing the expression of POMC gene.

adenosine 5'-monophosphate; adrenocorticotropin; energy homeostasis; pituitary; starvation