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This version published online on December 9, 2004
Endocrinology, doi:10.1210/en.2004-1202
A more recent version of this article appeared on March 1, 2005
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Submitted on September 10, 2004
Accepted on November 29, 2004

Regulation of Gene Expression in Magnocellular Neurons in rat supraoptic nucleus during sustained Hypoosmolality

Noriko Mutsuga, Tal Shahar, Joseph G. Verbalis, Charlie C. Xiang, Michael J. Brownstein, and Harold Gainer*

Laboratory of Neurochemistry, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA; Department of Medicine, Division of Endocrinology and Metabolism, Georgetown University, Washington, DC 20007, USA; Laboratory of Genetics, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA

* To whom correspondence should be addressed. E-mail: gainerh{at}ninds.nih.gov.

Hypoosmolality produces a dramatic inhibition of vasopressin (VP) and oxytocin (OT) gene expression in the supraoptic nucleus (SON). This study examines the effect of sustained hypoosmolality on global gene expression in the OT and VP magnocellular neurons (MCNs) of the hypothalamo-neurohypophysial system (HNS), to identify genes associated with the MCN's adaptation to this physiological condition. Using laser microdissection of the SON, T7 based linear amplification of its RNA, and a 35,319 element cDNA microarray, we compare gene expression profiles between SONs in normoosmolar (control), dDAVP-treated normoosmolar, and hypoosmolar rats. We found 4,959 genes with statistically significant differences in expression between normosmolar control and the hypoosmolar SONs, with 1,564 of these differing in expression by more than 2-fold. These genes serve a wide variety of functions, and most were up-regulated in gene expression in hypoosmolar compared with control SONs. Of these, 90 were preferentially expressed in the SON, and 44 coded for transcription-related factors, of which 15 genes were down-regulated and 29 genes were up-regulated in the hypoosmolar rat SONs. None of these transcription-related factor genes significantly changed in expression following sustained dDAVP-treatment alone, indicating that these changes were associated with the hypoosmolar state and not due solely to a decreased activity in the SON. Quantitative in situ hybridization histochemistry was selectively used to confirm and extend these microarray observations. These results indicate that the hypoosmolar state is accompanied by a global but selective increase in expression of a wide variety of regulatory genes in the SON.
Key words: hyponatremia • hypoosmotic • hyperosmotic • vasopressin • oxytocin • microarray • laser microdissection




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