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J. Biol. Chem., Vol. 278, Issue 21, 19280-19285, May 23, 2003
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From the
University Research Centre for Neuroendocrinology, University of Bristol, Bristol Royal Infirmary, Marlborough Street, Bristol BS2 8HW, United Kingdom,
|| DNA Array Unit, NIA, National Institutes of Health, Baltimore, Maryland 21224,
** Biotechnology and Germplasm Laboratory, United States Department of Agriculture, Beltsville, Maryland 20705
Physiological activation of the hypothalamo-neurohypophyseal system (HNS) by dehydration results is a massive release of vasopressin (VP) from the posterior pituitary. This is accompanied by a functional remodeling of the HNS. In this study we used cDNA arrays in an attempt to identify genes that exhibit differential expression in the hypothalamus following dehydration. Our study revealed nine candidate genes, including interleukin-6 (IL-6) as a putative novel secretory product of HNS worthy of further analysis. In situ hybridization and immunocytochemistry confirmed that IL-6 is robustly expressed in the supraoptic (SON) and the paraventricular (PVN) nuclei of the hypothalamus. By double staining immunofluorescence we showed that IL-6 is largely co-localized with VP in the SON and PVN. In situ hybridization, immunocytochemistry, and Western blotting all revealed IL-6 up-regulation in the SON and PVN following dehydration, thus validating the array data. The same dehydration stimulus resulted in an increase in IL-6 immunoreactivity in the axons of the internal zone of the median eminence and a marked reduction in IL-6-like material in the posterior pituitary gland. We thus suggest that IL-6 takes the samesecretory pathway as VP and is secreted from the posterior pituitary following a physiological stimulus.
Received for publication, September 26, 2002 , and in revised form, March 3, 2003.
To whom correspondence should be addressed. Present address: MRC Centre for Synaptic Plasticity, Dept. of Anatomy, School of Medical Sciences, University Walk, University of Bristol, Bristol BS8 1TD, UK. Tel.: 44-117-954-6477; Fax: 44-117-929-1687; E-mail: m.ghorbel{at}bris.ac.uk.
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