Transcription factor CREB3L1 mediates cAMP and glucocorticoid regulation of arginine vasopressin gene transcription in the rat hypothalamus. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Greenwood, Mingkwan; Greenwood, Michael; Mecawi, Andre; Loh, Su; Rodrigues, José; Paton, Julian; Murphy, David
• Is Part Of: Molecular brain. Volume 8:Issue 1(2015)
• Page Start: 1
• Page End: 12
• Publication Date: 2015-12
• Subjects: Transcription -- Forskolin -- Dexamethasone -- Hyperosmotic -- Magnocellular neuron -- Supraoptic nucleus -- Paraventricular nucleus -- AtT20 -- Rat -- Organotypic culture; Brain -- Periodicals; Molecular biology -- Periodicals; 573.86
• DOI: 10.1186/s13041-015-0159-1
• Languages: English
• ISSNs: 1756-6606

Abstract

Abstract Background Arginine vasopressin (AVP), a neuropeptide hormone that functions in the regulation of water homeostasis by controlling water re-absorption at kidneys, is synthesised in supraoptic nucleus and paraventricular nucleus of the hypothalamus. An increase in plasma osmolality stimulates secretion of AVP to blood circulation and induces AVP synthesis in these nuclei. Although studies on mechanism of AVP transcriptional regulation in hypothalamus proposed that cAMP and glucocorticoids positively and negatively regulateAvp expression, respectively, the molecular mechanisms have remained elusive. Recently, we identified CREB3L1 (cAMP-responsive element binding protein 3 like 1) as a putative transcription factor ofAvp transcription in the rat hypothalamus. However the mechanism of how CREB3L1 is regulated in response of hyperosmotic stress in the neurons of hypothalamus has never been reported. This study aims to investigate effect of previously reported regulators (cAMP and glucocorticoid) ofAvp transcription on transcription factor CREB3L1 in order to establish a molecular explanation for cAMP and glucocorticoids effect on AVP expression. Results The effect of cAMP and glucocorticoid treatment onCreb3l1 was investigated in both AtT20 cells and hypothalamic organotypic cultures. The expression ofCreb3l1 was increased in both mRNA and protein level by treatment with forskolin, which raises intracellular cAMP levels. Activation of cAMP by forskolin also increasedAvp promoter activity in AtT20 cells and this effect was blunted by shRNA mediated silencing ofCreb3l1 . The forskolin induced increase inCreb3l1 expression was diminished by combined treatment with dexamethasone, and, in vivo, intraperitoneal dexamethasone injection blunted the increasein Creb3l1 andAvp expression induced by hyperosmotic stress. Conclusion Here we shows that cAMP and glucocorticoid positively and negatively regulateCreb3l1 expression in the rat hypothalamus, respectively, and regulation of cAMP on AVP expression is mediated through CREB3L1. This data provides the connection between CREB3L1, a newly identified transcription factor of AVP expression, with the previously proposed mechanism ofAvp transcription which extends our understanding in transcription regulation ofAvp in the hypothalamus.