Regulation of stress-induced transcriptional changes in the hypothalamic neurosecretory neurons.
Transcriptional changes in corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) gene expression were studied by in situ hybridization histochemistry using cRNA probes directed against intronic sequences. Acute ether stress resulted in a rapid induction of CRF and a delayed activation of vasopressin heteronuclear (hn)RNA in the parvocellular neurosecretory neurons within the paraventricular nucleus (PVN) of the hypothalamus. To explore possible molecular mechanisms regulating stress-related neuropeptide expression in vivo, the time-courses of stress-induced activation of different transcription factor classes were compared to that of changes in neuropeptide transcription. The peak of CRF transcription was parallel to that of cAMP response-element binding protein (CREB) phosphorylation but preceded the induction of c-fos and NGFI-B mRNAs and Fos protein. In contrast, AVP expression occurred in step with immediate-early gene (IEG) responses, suggesting involvement of different mechanisms underlying stress-induced neuropeptide responses. The interference of glucocorticoid hormones with stress-induced neuropeptide and transcription-factor responses has also been revealed in rats acutely or chronically pretreated with glucocorticoids. Acute dexamethasone injection did not prevent neuropeptide and transcription factor responses to either inhalation, whereas chronic corticosterone administration completely blocked IEG and neuropeptide induction in the stress-related neurosecretory neurons.
Kovács
K J
KJ
Laboratory of Molecular Neuroendocrinology, Institute of Experimental Medicine, Budapest, Hungary.
Sawchenko
P E
PE
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics*; D003345:Corticosterone / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D004986:Ether / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects; D017781:Genes, Immediate-Early; D017403:In Situ Hybridization; D007438:Introns / Q000235:genetics; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D018075:RNA, Complementary / Q000235:genetics; D012332:RNA, Heterogeneous Nuclear / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000502:physiology; D011987:Receptors, Steroid; D013312:Stress, Physiological / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics; D014158:Transcription, Genetic
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D016760:Proto-Oncogene Proteins c-fos; D018075:RNA, Complementary; D012332:RNA, Heterogeneous Nuclear; D018160:Receptors, Cytoplasmic and Nuclear; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D014157:Transcription Factors; D004986:Ether; D001127:Arginine Vasopressin; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone