title: 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.
abstract: 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 beta, 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.
authors.affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol BS1 3NY, United Kingdom.
authors.forename: Jing
authors.initials: J
authors.lastname: Qiu
authors.forename: Song
authors.initials: S
authors.lastname: Yao
authors.forename: Charles
authors.initials: C
authors.lastname: Hindmarch
authors.forename: Vagner
authors.initials: V
authors.lastname: Antunes
authors.forename: Julian
authors.initials: J
authors.lastname: Paton
authors.forename: David
authors.initials: D
authors.lastname: Murphy
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003681:Dehydration / Q000378:metabolism*; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D009994:Osmolar Concentration; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013495:Supraoptic Nucleus / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C486721:Giot1 protein, rat; D051538:Hepatocyte Nuclear Factor 1-alpha; C496489:Hnf1a protein, rat; D012333:RNA, Messenger; D014157:Transcription Factors; C447180:Zfp347 protein, rat; D017868:Cyclic AMP-Dependent Protein Kinases