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Journal of Neuroscience, Vol 11, 585-599, Copyright © 1991 by Society for Neuroscience
Differential regulation of corticotropin-releasing factor mRNA in rat brain regions by glucocorticoids and stress
T Imaki, JL Nahan, C Rivier, PE Sawchenko and W Vale
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037.
The regulation of corticotropin-releasing factor (CRF) mRNA expression in
the rat brain by glucocorticoids and stress was examined by Northern blot
analysis and in situ hybridization histochemistry. Rats either were exposed
to a single electrical footshock session and killed 2, 4, 12, or 24 hr
later (acute stress), or were subjected to the same regimen twice daily for
3 or 7 d and killed on the day following the last session (chronic stress).
Rats placed in the experimental chamber but not administered shock
comprised a "sham-handling" group. Chronic (7 d) intermittent footshock
stress resulted in an 84 +/- 26% (P less than 0.05) increase in CRF mRNA
levels in the whole hypothalamus as detected by Northern blot analysis and
a 97 +/- 29% (P less than 0.05) increase in the paraventricular nucleus
(PVN) as detected using in situ hybridization. No significant change in CRF
mRNA levels was observed in the hypothalamus at any time up to 24 hr after
a single exposure to footshock stress. A different pattern of results was
obtained in other CRF-expressing cell groups. In Barrington's nucleus (a
pontine micturition center), both acute and chronic stress produced
significant increases in CRF mRNA, while in the olfactory bulb, both
paradigms resulted in decreased levels. By Northern blot analysis, CRF mRNA
in the olfactory bulb declined steadily, beginning at 4 hr after acute
stress, and reached significance at 24 hr (69.2 +/- 1.9% of control, P less
than 0.05). Levels from chronically (7 d) stressed animals declined to 54.1
+/- 5.1% of control value (P less than 0.05). Analysis of hybridization
histochemical material revealed that both the number of positively
hybridized cells and the number of silver grains per cell in the mitral and
external plexiform layers of the bulb decreased following acute and chronic
stress. However, CRF mRNA levels in the olfactory bulb were decreased to a
comparable extent in the sham- handling group, suggesting that exposure to
a novel environment can effect a decrease in CRF mRNA levels in the
olfactory bulb. To provide comparisons with the effects of manipulation of
glucocorticoid status, comparable analyses were carried out in separate
groups of animals following adrenalectomy (ADX) with and without
corticosteroid replacement. After ADX, CRF mRNA levels in the whole
hypothalamus increased 60 +/- 5% (P less than 0.05) and were normalized
following dexamethasone replacement. In contrast to the hypothalamus, no
effects of steroid manipulation on CRF mRNA levels in the olfactory bulb,
midbrain, cerebral cortex, or brain stem were detected.(ABSTRACT TRUNCATED
AT 400 WORDS)
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