SEQUENCE OF STRESS-INDUCED ALTERATIONS IN INDEXES OF SYNAPTIC AND TRANSCRIPTIONAL ACTIVATION IN PARVOCELLULAR NEUROSECRETORY NEURONS

Immediate-early genes (IEGs) are widely used to mark endocrine hypotha lamic neurons that are activated in response to stress, yet their rela tionship to the transcriptional control of relevant effector molecule expression is unclear. Acute ether stress provokes increased adrenocor ticotropic hormone (ACM) and corticosterone secretion that peaks at 5 and 30 min, respectively, after the challenge. Using probes complement ary to intronic sequences of genes encoding ACTH secretagogues in parv ocellular neurosecretory neurons of the paraventricular nucleus, we fo und these events to be accompanied by rapid and transient increases in corticotropin-releasing factor heteronuclear RNA (CRF hnRNA; peak al 5 min) and by a delayed upregulation of arginine vasopressin (AVP) hnR NA (120 min). To identify candidate mechanisms regulating peptide expr ession, we followed the timing of ether effects on representatives of three transcription factor classes: IEGs [c-fos and nerve growth facto r I-B (NGFl-B)], a POU-domain factor (Brn-2), and the cAMP response el ement-binding protein (CREB), using antisera specific to its transcrip tionally active, phosphorylated form (pCREB). After ether exposure, c- fos and NGFl-B mRNA induction were maximal at 30-60 min, whereas Fos p rotein peaked at 60-120 min. Bm-2 mRNA was expressed constitutively in the PVH and was unresponsive to stress. By contrast, pCREB was induce d in parvocellular neurons with a time course parallel to that of CRF hnRNA expression. Stress-induced transcriptional activation of the CRF and AVP genes in hypophysiotropic neurons follows distinct time cours es that are compatible with control mechanisms involving phosphorylati on events and de novo protein synthesis, respectively.