Endocrine Abstracts

Annexin-1 (ANXA1) is a 37 kDa calcium- and phospholipid-binding protein expressed abundantly in S100-positive folliculostellate (FS) cells in the anterior pituitary gland. ANXA1 is localised both intracellularly and on the cell surface in high density foci appearing at points of contact between the FS cells and the neighbouring secretory cells, where it has been demonstrated to mediate the glucocorticoid-induced negative feedback on the secretion of ACTH from corticotrophs. Glucocorticoids stimulate the externalisation of ANXA1 to the surface of FS cells (and the subsequent replenishment of intracellular ANXA1), which in turn act on cell surface receptors on adjacent secretory cells to inhibit release of ACTH. The cholinergic system has been implicated in inhibitory pituitary responses to immune or inflammatory stress and FS cells play an important role at the interface of the immune and endocrine systems. In addition, acetylcholine (ACh) has been demonstrated to increase intracellular Ca²⁺ in FS cells in the rat pituitary via activation of muscarinic M₁ receptors and phospholipase C activation¹ but it is not known if this stimulates release of FS bioactive mediators or if nicotinic receptors are involved. By use of immunofluorescence microscopy and western blot analysis to measure ANXA1 we have investigated the effects of ACh on the cellular distribution of ANXA-1 in the TtT/GF FS cell line. We also investigated the effects of choline, an agonist at alpha7-nicotinic receptors. TtTGF cells were incubated for 3 h with either ACh (0.05–200 μM), choline (0.05–200 μM) or positive control dexamethasone (100 nM). Both ACh and choline concentration-dependently stimulated the externalisation of ANXA1from TtTGF cells. Furthermore, we have also demonstrated the expression and secretion of the enzyme acetycholinesterase (AChE) from TtT/GF cells. All these findings suggest a participation of a cholinergic mechanism in the control of ANXA1 release from FS cells.

Reference: 1. Nakajima Y et al. American Journal of Physiology Endocrinology and Metabolism 2001 280 E608–E615.