Endocrine Abstracts

Annexin 1 (ANXA1) was first identified as a glucocorticoid (GC)-inducible protein in macrophages and is a mediator of the powerful anti-inflammatory actions of these steroid hormones. In the pituitary ANXA1 plays a critical role in mediating the early-onset negative feedback effects of GCs on the release of ACTH. ANXA1 is expressed in abundance in the anterior pituitary gland where it is localized specifically to the S100-positive folliculo-stellate (FS) cells. GCs act on FS cells to cause translocation of ANXA1 to the plasma membrane, with particular accumulation at points where the cells make contact with adjacent secretory cells. The released protein then acts via cell surface receptors on the adjacent secretory cells to suppress stress-evoked ACTH release. ANXA1 lacks a cleavable signal sequence and its secretion is not affected by inhibitors of the classical secretory pathway. We have demonstrated a role for the ATP binding cassette transporter, ABCA1, as a ‘non-classical’ transport pathway for ANXA1 export from FS cells. In monocytes a class of anti-allergic drugs, the cromolyns, enhance the release of ANXA1 when stimulated with glucocorticoid. Using western blot analysis, immunofluorescence and electron microscopic techniques in a FS model system, TtT/GF cells, we investigated the effect of the cromolyn anti-allergic drugs di-sodium cromoglycate (4 μM–4 mM) and sodium nedocromil (4 μM) on the trafficking and release of ANXA1 when triggered by dexamethasone treatment (3 h, 100 nM). When administered alone, cromoglycate or nedocromil had no effect on ANXA1 release however, in the presence of a fixed sub-maximal concentration of dexamethasone, increasing amounts of the cromoglycate-like drugs caused a significant (P<0.01, n=3) enhancement of ANXA1 release. Therefore, although control of peripheral ANXA1 secretion is thought of as the mechanism of action of cromolyn anti-allergy drugs, in the pituitary such drugs enhance the negative feedback actions of GCs.