The Journal of Neuroscience, July 15, 2002, 22(14):6282-6289
Interactions between Heterotypic Stressors and Corticosterone
Reveal Integrative Mechanisms for Controlling Corticotropin-Releasing
Hormone Gene Expression in the Rat Paraventricular Nucleus
Alan G.
Watts and
Graciela
Sanchez-Watts
The Neuroscience Program and the Department of Biological
Sciences, University of Southern California, Los Angeles, California
90089-2520
Although the convergence of neural and humoral afferent information
onto paraventricular neuroendocrine corticotropin-releasing hormone
(CRH) neurons is a major determinant for adaptive stress responses, the
underlying integrative mechanisms are poorly understood. To dissect the
relative contributions made by neural afferents and corticosterone to
these processes, we determined how the concurrent application of two
heterotypic physiological stressors, chronic dehydration (produced by
drinking hypertonic saline) and sustained hypovolemia (produced by
subcutaneous injections of polyethylene glycol), is interpreted by the
synthetic and secretory activity of CRH neurons using in
situ hybridization and plasma ACTH measurements. These two
stressors are encoded by relatively simple, distinct, and well defined
sets of neural afferents to CRH neurons. Both increase plasma
corticosterone, but they have opposing actions on CRH
gene expression when applied separately. In the first
experiment, we showed that chronic dehydration suppresses
CRH gene transcription after hypovolemia, but not the
preproenkephalin and c-fos mRNA responses or ACTH
secretion. In the second, we showed that negative feedback actions of
corticosterone do not suppress CRH gene activation after
hypovolemia, but instead determine the prestress lower limit of a range
within which the CRH gene then responds. Collectively, these data show
that at least two processes are integrated to control how the
CRH gene responds to multiple stimuli. First, the
presence of corticosterone, which although permissive for appropriately
activating the CRH gene during hypovolemia, does not mediate the
suppressed gene response. Second, neural afferent-driven processes that
encode dehydration play a central role in suppressing CRH activation.
Key words:
corticosterone; stress; adaptation; integration; neuropeptides; afferent control
Copyright © 2002 Society for Neuroscience 0270-6474/02/22146282-08$05.00/0
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