The Journal of Neuroscience, September 1, 1999, 19(17):7640-7647
Nitric Oxide Stimulates ACTH Secretion and the Transcription of
the Genes Encoding for NGFI-B, Corticotropin-Releasing Factor,
Corticotropin-Releasing Factor Receptor Type 1, and Vasopressin in the
Hypothalamus of the Intact Rat
Soon
Lee,
C. Kwon
Kim, and
Catherine
Rivier
The Clayton Foundation Laboratories for Peptide Biology, The Salk
Institute, La Jolla, California 92037
We investigated the effect of the intracerebroventricular
injection of the nitric oxide (NO) donor 3-morpholino-sydnonimine (SIN-1) on the release of adrenocorticotropin hormone (ACTH) and the
neuronal response of hypothalamic neurons responsible for this release.
Rats that were administered SIN-1 showed significant elevations in
plasma ACTH levels, a response that was virtually abolished by
antibodies against corticotropin-releasing factor (CRF) and
significantly blunted by vasopressin (VP) antiserum. SIN-1 also
upregulated heteronuclear (hn) transcripts for CRF and VP and messenger
RNA (mRNA) levels for the immediate early gene NGFI-B and for
CRF receptor type 1 (CRF-R1) in the parvocellular portion of the paraventricular nucleus (PVN) of the hypothalamus. Blockade of prostaglandin synthesis with ibuprofen did not alter the
ACTH or the PVN response to SIN-1. The central nucleus of the amygdala
and the supraoptic nucleus, regions that are involved in autonomic
adjustments to altered cardiovascular activity, also responded to SIN-1
with elevated NGFI-B mRNA levels. However, the only change in mean
arterial blood pressure caused by this NO donor was a transient and
modest increase. To our knowledge, this is the first demonstration that
in the intact rat NO stimulates the activity of PVN neurons that
control the hypothalamic-pituitary-adrenal axis. It must be noted,
however, that our results do not allow us to determine whether this
effect was direct or mediated through PVN afferents. This study should
help resolve the controversy generated by the use of isolated brain
tissues to investigate the net effect of NO on hypothalamic peptide production.
Key words:
nitric oxide; PVN; ACTH; CRF; vasopressin; HPA axis
Copyright © 1999 Society for Neuroscience 0270-6474/99/19177640-08$05.00/0