Lipocortin-1 inhibits crh stimulation of plasma acth and il
-1[beta]-stimulated hypothalamic crh release in the rat.
Sudlow, Allan W., Frank Carey, Robert Forder, and Nancy J. Rothwell.
School of Biological Sciences, University of Manchester, Oxford
Rd., Manchester, M13 9PT; Zeneca Pharmaceuticals, Macclesfield,
Cheshire, SK10 4TG
APStracts 2:0265R, 1995.
A 188 amino acid N-terminal fragment of recombinant human lipocortin-1
(rhLC-1) (LC-1 fragment) mimics glucocorticoid (and rhLC-1)
inhibition of (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. Co-injection 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(IL)-1[beta]. Central injection of the CRH functional
analogue sauvagine led to a 46% reduction (P>0.05, two-way
ANOVA) in rat hypothalamic irCRH content which was reversed by co
-injection 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.
Received 17 April 1995; accepted in final form 18 July 1995.
APS Manuscript Number R239-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95