Endocrine Abstracts

Annexin A1 - a unique mediator of glucocorticoid action.

Annexin A1 is a 37 KD protein found in a variety of differentiated cell types in the mammalian body. It is a member of a super family of proteins known as the annexins of which approximately 13 are found in mammals. Annexin A1 is one of the most studied members of this family and appears to play a key role in mediating the effects of glucocorticoid hormones and drugs on the immune and neuro-endocrine systems.

In cells such as the macrophage, treatment with glucocorticoids both increases the transcription and the translation of the annexin A1 gene but also causes the phosphorylation at sites in the N-terminus, of pre-existing intracellular pools of the protein. Such phosphorylated species are externalised to the cell surface where they can act in a paracrine or autocrine fashion by binding to receptors which are most probably of the FPR family.

This process is crucial to the development of some actions of glucocorticoids as the administration of the appropriate anti-sense mRNA or neutralising anti-bodies can abolish several glucocorticoid effects. Conversely, administration of the full length protein itself, or fragments from the key biologically active N-terminal region, can produce glucocorticoid-like actions and rescue the phenotype caused by the deletion of the annexin A1 gene. Annexin A1 null mice also display an exacerbated response to inflammatory stimuli and a partial resistance to glucocorticoids.

Annexin A1 is a fascinating key player in the physiology and pharmacology of glucocorticoid hormones and drugs.

RJF is a Wellcome Trust Principal Research Fellow.