Opposing influences of glucocorticoids and interleukin‐1β on the secretion of growth hormone and ACTH in the rat in vivo: role of hypothalamic annexin 1

This study exploited established immunoneutralization protocols and an N-terminal annexin 1 peptide (annexin 1Ac2 – 26) to advance our knowledge of the role of annexin 1 as a mediator of acute glucocorticoid action in the rat neuroendocrine system in vivo. Rats were treated with corticosterone (500 μg kg−1, i.p.) or annexin 1Ac2 – 26 (0.1 – 10 ng rat−1, i.c.v.) and 75 min later with interleukin 1β (IL-1β, 10 ng rat−1, i.c.v. or 500 μg kg−1, i.p). Blood was collected 1 h later for hormone immunoassay. Where appropriate, anti-annexin 1 polyclonal antiserum (pAb) was administered subcutaneously or centrally prior to the steroid challenge. Corticosterone did not affect the resting plasma corticotrophin (ACTH) concentration but suppressed the hypersecretion of ACTH induced by IL-1β (i.p. or i.c.v.). Its actions were quenched by anti-annexin 1 pAb (s.c. or i.c.v) and mimicked by annexin 1Ac2 – 26. By contrast, corticosterone provoked an increase in serum growth hormone (GH) which was ablated by central but not peripheral administration of anti-annexin 1 pAb. IL-1β (i.c.v. or i.p.) did not affect basal GH but, when given centrally but not peripherally, it abolished the corticosterone-induced hypersecretion of GH. Annexin 1Ac2 – 26 (i.c.v.) also produced an increase in serum GH which was prevented by central injection of IL-1β. The results support the hypothesis that the acute regulatory actions of glucocorticoids on hypothalamo-pituitary-adrenocortical function require annexin 1. They also provide novel evidence that the positive influence of the steroids on GH secretion evident within this timeframe is effected centrally via an annexin 1-dependent mechanism which is antagonized by IL-1β. British Journal of Pharmacology (2001) 134, 887–895; doi:10.1038/sj.bjp.0704324