AJP - Regulatory, Integrative and Comparative Physiology, Vol 270, Issue 1 54-R60, Copyright © 1996 by American Physiological Society
Lipocortin-1 inhibits CRH stimulation of plasma ACTH and IL-1 beta-stimulated hypothalamic CRH release in rats
A. W. Sudlow, F. Carey, R. Forder and N. J. Rothwell
School of Biological Sciences, University of Manchester, United Kingdom.
A 188-amino acid NH2-terminal fragment of recombinant human lipocortin-1
(rhLC-1) (LC-1 fragment) mimics glucocorticoid (and rhLC-1) inhibition of
corticotrophin-releasing hormone (CRH)-stimulated release of
adrenocorticotrophin (ACTH) from rat anterior pituitary and
cytokine-stimulated CRH release from rat hypothalamus in vitro. The present
in vivo study examined the effect of LC-1 fragment on CRH stimulation of
rat plasma ACTH and release of rat hypothalamic CRH. Coinjection of LC-1
fragment inhibited the increase in plasma ACTH concentration stimulated by
either central (76% inhibition) or peripheral (72% inhibition) injection of
CRH and abolished the (62%) depletion of hypothalamic immunoreactive
(ir)CRH stimulated by central injection of interleukin-1 beta. Central
injection of the CRH functional analogue sauvagine led to a 46% reduction
(P > 0.05, 2-way analysis of variance) in rat hypothalamic irCRH
content, which was reversed by coinjection of LC-1 fragment. These results
indicate that LC-1 can suppress the activity of the hypothalamic-pituitary
axis in the rat, possibly by inhibiting a positive feedback mechanism
controlling release of hypothalamic CRH.
