This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart 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 PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nikodemova, M. Articles by Aguilera, G. Search for Related Content PubMed PubMed Citation Articles by Nikodemova, M. Articles by Aguilera, G.

Cyclic Adenosine 3',5'-Monophosphate Regulation of Corticotropin-Releasing Hormone Promoter Activity in AtT-20 Cells and in a Transformed Hypothalamic Cell Line

Section on Endocrine Physiology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development (M.N., G.A.), and Pulmonary/Critical Care Medicine Branch, National Heart, Lung, and Blood Institute (V.M.), National Institutes of Health, Bethesda, Maryland 20892; and Department of Psychiatry, University of Cincinnati (J.K.), Cincinnati, Ohio 45267

Address all correspondence and requests for reprints to: Dr. Greti Aguilera, Section on Endocrine Physiology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Building 10, Room 10N 262, 10 Center Drive, MSC 1862, Bethesda, Maryland 20892-1862. E-mail: greti{at}helix.nih.gov.

The regulation of CRH promoter activity by cAMP was studied in two cell lines, the pituitary corticotroph cell line AtT-20 and the immortalized hypothalamic cell line 4B, which expresses CRH and vasopressin. In 4B cells transfected with a CRH promoter-luciferase construct, the adenylyl cyclase stimulator, forskolin, increased luciferase activity in parallel with increases in intracellular cAMP. In 4B cells, however, the phosphodiesterase inhibitor, isobutylmethylxanthine, potentiated forskolin-stimulated cAMP without affecting further increases in luciferase activity. In AtT-20 cells, forskolin plus isobutylmethylxanthine elevated cAMP only slightly, but increased luciferase activity to levels similar to those observed in 4B cells. AtT-20 cells were also unresponsive to 8-bromo-cAMP, due in part to higher phosphodiesterase (PDE) activities. Although both cells contained PDE1, -3, and -4, inhibition of either PDE4 or PDE1 potentiated luciferase activity stimulated by submaximal forskolin concentrations in 4B cells, while only simultaneous inhibition of PDE3 and PDE4 was effective in AtT-20 cells. The data show that minor elevations in intracellular cAMP are sufficient for full stimulation of CRH promoter activity regardless of the cell line. Furthermore, poor CRH promoter activation in AtT-20 cells appears to result from deficient cAMP production and rapid cAMP degradation by PDE.

This article has been cited by other articles:

				Y. Liu, A. Kamitakahara, A. J. Kim, and G. Aguilera Cyclic Adenosine 3',5'-Monophosphate Responsive Element Binding Protein Phosphorylation Is Required But Not Sufficient for Activation of Corticotropin-Releasing Hormone Transcription Endocrinology, July 1, 2008; 149(7): 3512 - 3520. [Abstract] [Full Text] [PDF]

				K. Kageyama, K. Hanada, Y. Iwasaki, S. Sakihara, T. Nigawara, J. Kasckow, and T. Suda Pituitary adenylate cyclase-activating polypeptide stimulates corticotropin-releasing factor, vasopressin and interleukin-6 gene transcription in hypothalamic 4B cells J. Endocrinol., November 1, 2007; 195(2): 199 - 211. [Abstract] [Full Text] [PDF]

				I. Murakami, S. Takeuchi, T. Kudo, S. Sutou, and S. Takahashi Corticotropin-releasing hormone or dexamethasone regulates rat proopiomelanocortin transcription through Tpit/Pitx-responsive element in its promoter J. Endocrinol., May 1, 2007; 193(2): 279 - 290. [Abstract] [Full Text] [PDF]

				M. Yao, M. Stenzel-Poore, and R. J. Denver Structural and Functional Conservation of Vertebrate Corticotropin-Releasing Factor Genes: Evidence for a Critical Role for a Conserved Cyclic AMP Response Element Endocrinology, May 1, 2007; 148(5): 2518 - 2531. [Abstract] [Full Text] [PDF]

				J. D. Shepard, Y. Liu, P. Sassone-Corsi, and G. Aguilera Role of Glucocorticoids and cAMP-Mediated Repression in Limiting Corticotropin-Releasing Hormone Transcription during Stress J. Neurosci., April 20, 2005; 25(16): 4073 - 4081. [Abstract] [Full Text] [PDF]