Glucocorticoids modulate the cellular disposition of lipocortin 1 in the rat brain in vivo and in vitro

Abstract

The role of glucocorticoids in the regulation of lipocortin 1 (LC1) mRNA/protein expression in the brain is uncertain. This study has examined the influence of dexamethasone on the disposition of LC1 protein in various central and peripheral tissues in the rat. LC1 was readily detectable in all tissues studied by Western blot analysis. Exposure to dexamethasone in vitro (0.1 microM, 3 h) or in vivo (20 micrograms/100 g i.p., 24 h before autopsy) had no discernible effects on intracellular LC1 levels but increased the amount of LC1 attached to the outer surface of cells (pericellular LC1) in cortex, hippocampus, hypothalamus, pituitary gland and peritoneal macrophages (in vitro only). The results suggest that in central tissues, as in the periphery, glucocorticoids promote the translocation of LC1 from intracellular to pericellular sites.

Annexin-1 Regulates Growth Arrest Induced by High Levels of Estrogen in MCF-7 Breast Cancer Cells

“…Evidence associating ANXA1 expression and function with glucocorticoid treatment is indisputable (21)(22)(23)28). This induction of ANXA1 expression can be blocked by the glucocorticoid receptor antagonist RU486 (29).…”

“…Its endogenous function is still under debate, but most have focused on its anti-inflammatory actions, shown to mimic those of glucocorticoids (20). ANXA1 is glucocorticoid-inducible (21)(22) through transcriptional activation of the glucocorticoid response element as well as through rapid de novo synthesis (23). Glucocorticoids were not effective in ANXA1-deficient mice in two models of acute inflammation, suggesting that ANXA1 could be the endogenous protein mediating the anti-inflammatory actions of glucocorticoids (24).…”

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

“…It is found in abundance in the anterior pituitary gland (Smith et al, 1993;Taylor et al, 1993), particularly in the S100-positive folliculo-stellate cells (Traverso et al, 1999), and also in speci®c loci in the hypothalamus, including the median eminence and the paraventricular, arcuate and periventricular nuclei (Smith et al, 1993). Moreover, its expression and cellular disposition in these tissues are regulated by glucocorticoids (Loxley et al, 1993b;Taylor et al, 1993;Philip et al, 1997;Christian et al, 1999). To date, the evidence that annexin 1 ful®ls a functional role as a mediator of the early inhibitory actions of the GCs on HPA function (i.e.…”

Evidence from immunoneutralization and antisense studies that the inhibitory actions of glucocorticoids on growth hormone release in vitro require annexin 1 (lipocortin 1)

“…It was ®rst identi®ed as a potential mediator of the therapeutically important antiin¯ammatory actions of the GCs and has since been shown to contribute to the signalling mechanisms e ecting the regulatory actions of the steroids in the neuroendocrine system (reviewed in . Annexin 1 is found in abundance in the anterior pituitary gland, particularly in the S100-positive folliculo-stellate cells, and in speci®c loci in the hypothalamus where its expression and cellular disposition are regulated by GCs (Smith et al, 1993;Philip et al, 1997;Christian et al, 1999;Traverso et al, 1999). GCs thus induce de novo synthesis of annexin 1 in these tissues; they also promote the exportation of the newly synthesized protein from the cytoplasm to a pericellular site where it adheres to the cell membrane by a Ca 2+ -dependent mechanism (Taylor et al, 1993;Philip et al, 1997).…”

“…Annexin 1 is found in abundance in the anterior pituitary gland, particularly in the S100-positive folliculo-stellate cells, and in speci®c loci in the hypothalamus where its expression and cellular disposition are regulated by GCs (Smith et al, 1993;Philip et al, 1997;Christian et al, 1999;Traverso et al, 1999). GCs thus induce de novo synthesis of annexin 1 in these tissues; they also promote the exportation of the newly synthesized protein from the cytoplasm to a pericellular site where it adheres to the cell membrane by a Ca 2+ -dependent mechanism (Taylor et al, 1993;Philip et al, 1997). Functional studies in which neutralizing antisera, antisense oligodeoxynucleotides (ODNs) and various annexin 1 related peptides have been used as probes, have identi®ed a key role for annexin 1 in e ecting the acute inhibitory actions of the GCs on the secretion of corticotrophin (ACTH) and its principal hypothalamic releasing hormone (CRH, Loxley et al, 1993;Taylor et al, 1993;1995b;.…”