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The Journal of Neuroscience, February 28, 2007, 27(9):2196-2203; doi:10.1523/JNEUROSCI.5420-06.2007

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Cellular/Molecular
Transcription Factor Expression in the Hypothalamo-Neurohypophyseal System of the Dehydrated Rat: Upregulation of Gonadotrophin Inducible Transcription Factor 1 mRNA Is Mediated by cAMP-Dependent Protein Kinase A

Jing Qiu,¹ Song Yao,¹ Charles Hindmarch,¹ Vagner Antunes,¹ Julian Paton,² and David Murphy¹

¹Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol BS1 3NY, United Kingdom, and ²Department of Physiology, Bristol Heart Institute, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom

Correspondence should be addressed to David Murphy, Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK. Email: d.murphy{at}bristol.ac.uk

The supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamo-neurohypophyseal system (HNS) undergo a dramatic function-related plasticity during dehydration. We hypothesize that alterations in steady-state transcript levels might be partially responsible for this remodeling. In turn, regulation of transcript abundance might be mediated by transcription factors. We used microarrays to identify changes in the expression of mRNAs encoding transcription factors in response to water deprivation in the SON. We observed downregulation of 10 and upregulation of 28 transcription factor transcripts. For five of the upregulated mRNAs, namely gonadotropin inducible ovarian transcription factor 1 (Giot1), Giot2, cAMP-responsive element binding protein 3-like 1, CCAAT/enhancer binding protein ß, and activating transcription factor 4, in situ hybridization was used to confirm the array results, demonstrating a significant increase in expression in SON and PVN magnocellular neurons (MCNs) after 3 d of water deprivation and, in some cases, upregulation in parvocellular PVN neurons. Using a viral vector expressing a potent inhibitor of cAMP-dependent protein kinase A (PKA), we show that the osmotically induced increase in the abundance of transcripts encoding Giot1 is mediated in vivo by the PKA pathway. We thus suggest that signaling pathways activated by dehydration in MCNs mediate transcription factor gene activation, which, in turn, regulate target genes that mediate HNS remodeling.

Key words: supraoptic nucleus; paraventricular nucleus; osmotic stress; plasticity; microarray; in situ hybridization; transcription factors; protein kinase A; viral vector

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Received Oct. 12, 2006; revised Jan. 15, 2007; accepted Jan. 15, 2007.

Correspondence should be addressed to David Murphy, Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK. Email: d.murphy{at}bristol.ac.uk

This article has been cited by other articles:

				S. S. Gouraud, K. Heesom, S. T. Yao, J. Qiu, J. F. R. Paton, and D. Murphy Dehydration-Induced Proteome Changes in the Rat Hypothalamo-Neurohypophyseal System Endocrinology, July 1, 2007; 148(7): 3041 - 3052. [Abstract] [Full Text] [PDF]

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