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Lipocortin-1 inhibits CRH stimulation of plasma ACTH and IL-1 beta-stimulated hypothalamic CRH release in rats.
Sudlow A, Carey F, Forder R, Rothwell NJ
Am J Physiol. 1996;270( 1 Pt 2):R54-60.
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Abstract
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.
Keyword(s)
Animals; Human; Immunoradiometric Assay; Male; Osmolar Concentration; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Support, Non-U.S. Gov't; antagonists & inhibitors: Corticotropin-Releasing Hormone; blood: Corticotropin; metabolism: Hypothalamus; pharmacology: Annexin I; pharmacology: Interleukin-1; pharmacology: Peptide Fragments; pharmacology: Peptides