Endocrine Abstracts

Annexin 1 (ANXA1) plays an important role in mediating the negative feedback effects of glucocorticoids on the HPA axis. In the anterior pituitary gland ANXA1 is localised mainly to the non-secretory folliculostellate (FS) cells. It is released from these cells by glucocorticoids and acts locally to suppress ACTH release from corticotrophs. Functional and histological studies suggest that the steroid-induced translocation of ANXA1 across the FS cell membrane is effected via membrane ABC A1 transport protein following activation of a kinase cascade¹. However, some drugs which block ABC A1 (e.g. the sulphonyurea glyburide), and hence, ANXA1 release from FS cells, also block SUR2B/Kir6.1 ATP-sensitive K⁺ channels (K⁺ _ATP channels). It is thus possible that these channels also contribute to the mechanisms effecting ANXA release. To test this hypothesis, we have explored the effects of drugs which open or block these channels on ANXA1 release, using a murine FS cell line (TtT/GF) known to express SUR2B/Kir6.1 K⁺ _ATP channels as a model. TtT/GF cells, maintained in standard conditions, were treated with dexamethasone and/or drugs which open (minoxidil or cromakalim) or close (sulphonyureas, e.g. glipizide) K⁺ _ATP channels. ANXA1 associated with the outer cell-membrane was determined by western blot analysis. Dexamethasone (10 nM) caused, within 90 min, an increase in cell surface ANXA1. Its effects were abolished by glipizide (100 micromolar) which alone had no effect on cell surface ANXA1. Minoxidil and cromakalim (1 to 100 micromolar) also caused translocation of ANXA1 to the cell surface. Their actions were (a) concentration-dependent, (b) additive with those of dexamethasone and (c) reversed in a concentration-dependent manner by glipizide (50 and 100 micromolar). The results suggest that SUR2B/Kir 6.1 K⁺ _ATP channels contribute to the mechanisms regulating the release of ANXA1 from FS cells.

Generously supported by the Wellcome Trust

1. John et al (2004) Trends in Endocrinology, 15, 103-109