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) inhibit ion of corticotrophin-releasing hormone (CRH)-stimulated release of ad renocorticotrophin (ACTH) from rat anterior pituitary and cytokine-sti mulated CRH release from rat hypothalamus in vitro. The present in viv o 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 stimulate d by either central (76% inhibition) or peripheral (72% inhibition) in jection of CRH and abolished the (62%) depletion of hypothalamic immun oreactive (ir)CRH stimulated by central injection of interleukin-1 bet a. Central injection of the CRH functional analogue sauvagine led to a 46% reduction (P > 0.05, 2-way analysis of variance) in rat hypothala mic irCRH content, which was reversed by coinjection of LC-1 fragment. These results indicate that LC-1 can suppress the activity of the hyp othalamic-pituitary axis in the rat, possibly by inhibiting a positive feedback mechanism controlling release of hypothalamic CRH.