Glucocorticoid group - Key achievements in the last decade.

• Identification of annexin 1 (formerly called lipocortin 1) as an essential mediator of the ‘early’ phase of glucocorticoid feedback in the hypothalamus and pituitary gland.

• Discovery that annexin 1 also mediates the early regulatory actions of glucocorticoids on the secretion of prolactin, TSH, GH, LH and testosterone.

• Discovery that (a) annexin 1 is produced almost exclusively by non-endocrine cells in the neuroendocrine system and (b) its glucocorticoid-induced inhibitory actions on peptide release are effected via a juxtacrine/paracrine mechanism involving activation of a kinase cascade and translocation of serine-phosphorylated species of annexin 1 across the cell membrane of folliculostellate cells. 






• Discovery that transport of ANXA1 across the cell membrane occurs via an ATP binding cassette transporter protein (ACBA1) and that the exported protein interacts with receptors on the surface of endocrine cells which are distinct from, but may be related to, the formyl peptide receptor.

• Partial dissociation of the anti-inflammatory and anti-secretory properties of annexin 1.

• Development and phenotypic characterisation of an annexin 1-null mouse; discovery that in addition to showing the predicted changes in host-defence and neuroendocrine function, this mouse also shows unexpected sexual dimorphisms and alterations in brain and pituitary morphology.

• Discovery of abnormal patterns of annexin 1 expression and phosphorylation in (a) patients with disorders of the HPA axis, (b) pituitary adenomas and (c) pituitary carcinoma and high grade glioma.

• Demonstration of anti-proliferative and pro-apoptotic actions of annexin 1 in in vitro models.

• Discovery that the long-term changes in HPA activity induced by early life glucocorticoid treatment are associated with disturbances in annexin-1 dependent glucocorticoid feedback and with pronounced morphological changes in the pituitary gland and brain and in the pulmonary host defence system.

• New insights to the roles of eicosanoids, cytokines, nitric oxide, adenosine, phosphodiesterases and phopholipase C in the control of the secretion of ACTH, CRH and AVP in adulthood and during development.

• Discovery of mechanisms of reciprocal communication between the thymus and the neuroendocrine system.