Endocrine Abstracts

Annexin 1 (Anx-1), a 37kDa protein, is a member of the super-family of Ca ²⁺ and phospholipid-binding annexin proteins and acts as a mediator of glucocorticoid (GC) action in the host defense and neuroendocrine systems. In the anterior pituitary Anx-1 is expressed mainly by folliculostellate (FS) cells and mediates the early delayed feedback inhibition exerted by GCs on the release of ACTH and other pituitary hormones. It has been previously demonstrated that TtT/GF cells (mouse pituitary-derived FS cells) express and externalize Anx-1 in response to GC ¹. However, Anx-1 lacks a cleavable signal sequence and the externalization was not affected by inhibitors of the secretory pathway ². We have previously shown that glyburide, an inhibitor of ATP-binding cassette (ABC) transporters inhibited the externalization of Anx-1 from TtT/GF cells ³. Here we investigated the mechanism of Anx-1 externalization from TtT/GF cells by ABCA1. Unlike glyburide, the use of selective ABCA1 inhibitors such as geranyl-geranyl pyrophosphate (GGPP) and sulfobromopthalein (SBP) did not markedly decrease Anx-1 externalization. Furthermore, it was found that silencing ABCA1 expression in TtT/GF cells by siRNA did not affect Anx-1 externalization. This was further confirmed by investigating Anx-1 externalization from pituitaries from ABCA1 knock out mice, where the knockout mice were found to externalize Anx-1 normally. However, since compensation by other ABC family members may occur in vivo, Anx-1 externalization was studied in zenopus oocytes injected with ABCA1 mRNA. The ABCA1 expressing oocytes were found to efficiently externalize endogenous Anx-1 providing good evidence for a role of ABCA1 in Anx-1 export.