Lipocortin-1 inhibits CRH stimulation of plasma ACTH and IL-1 beta-stimulated hypothalamic CRH release in rats.
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.
Sudlow
A W
AW
School of Biological Sciences, University of Manchester, United Kingdom.
Carey
F
F
Forder
R
R
Rothwell
N J
NJ
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D029845:Amphibian Proteins; D000818:Animals; D017305:Annexin A1 / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D015592:Immunoradiometric Assay; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000494:pharmacology; D036361:Peptide Hormones; D010455:Peptides / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins
D029845:Amphibian Proteins; D017305:Annexin A1; D007375:Interleukin-1; D010446:Peptide Fragments; D036361:Peptide Hormones; D010455:Peptides; D011994:Recombinant Proteins; C025727:sauvagine; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone