Journal of Neuroscience, Vol 7, 2807-2810, Copyright © 1987 by Society for Neuroscience
Hypophysectomy increases vasoactive intestinal peptide-stimulated cyclic AMP generation in the hippocampus of the rat
AL Harrelson and BS McEwen
In investigating the feedback effects of circulating hormones on the brain,
we showed previously that adrenalectomy (ADX) increases vasoactive
intestinal peptide (VIP)-stimulated cAMP generation in slices from rat
hippocampus, a brain structure with high levels of glucocorticoid
receptors. This effect is reversed by replacement with glucocorticoids such
as dexamethasone (DEX) and corticosterone (CORT). Here we report that, like
ADX, hypophysectomy (HYPOX) also elevates VIP- stimulated cAMP generation,
compared with sham-operated controls. Moreover, like glucocorticoid
replacement, administration of ACTH to HYPOX rats causes a decrease in cAMP
stimulation by VIP. Furthermore, ACTH had no effect when given to HYPOX +
ADX rats, indicating that the effects of ACTH require the presence of
adrenal steroid secretion. However, we find that ACTH may have a permissive
role in this glucocorticoid effect because, in the absence of the
pituitary, DEX treatment does not decrease VIP-stimulated cAMP levels in
the hippocampus. In addition, hippocampal beta-adrenergic-stimulated cAMP
accumulation was not suppressed by DEX treatment of HYPOX rats, which again
is different from the effect of DEX treatment on ADX animals. These results
are discussed in terms of possible synergism between pituitary hormones and
steroid hormones in exerting feedback actions on brain function.