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Journal of Neuroscience, Vol 16, 262-273, Copyright © 1996 by Society for Neuroscience
Sequence of stress-induced alterations in indices of synaptic and transcriptional activation in parvocellular neurosecretory neurons
KJ Kovacs and PE Sawchenko
Laboratory of Neuronal Structure and Function, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Immediate-early genes (IEGs) are widely used to mark endocrine hypothalamic
neurons that are activated in response to stress, yet their relationship to
the transcriptional control of relevant effector molecule expression is
unclear. Acute ether stress provokes increased adrenocorticotropic hormone
(ACTH) and corticosterone secretion that peaks at 5 and 30 min,
respectively, after the challenge. Using probes complementary to intronic
sequences of genes encoding ACTH secretagogues in parvocellular
neurosecretory neurons of the paraventricular nucleus, we found these
events to be accompanied by rapid and transient increases in
corticotropin-releasing factor heteronuclear RNA (CRF hnRNA; peak at 5 min)
and by a delayed upregulation of arginine vasopressin (AVP) hnRNA (120
min). To identify candidate mechanisms regulating peptide expression, we
followed the timing of ether effects on representatives of three
transcription factor classes: IEGs [c-fos and nerve growth factor I-B
(NGFI-B)], a POU-domain factor (Brn-2), and the cAMP response
element-binding protein (CREB), using antisera specific to its
transcriptionally active, phosphorylated form (pCREB). After ether
exposure, c-fos and NGFI-B mRNA induction were maximal at 30--60 min,
whereas Fos protein peaked at 60--120 min. Brn-2 mRNA was expressed
constitutively in the PVH and was unresponsive to stress. By contrast,
pCREB was induced 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
courses that are compatible with control mechanisms involving
phosphorylation events and de novo protein synthesis, respectively.
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