Annexin A1 (AnxA1) acts as a mediator of glucocorticoid (GC) actions in 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 release of ACTH and other pituitary hormones. GC cause the externalization of AnxA1. The stress responsiveness of the female rat hypothalamo-pituitary-adrenal system varies with the estrous cycle, with increased CORT release in response to stress at proestrus (Viau 1991). Anterior pituitary Anx-l levels vary with the estrous cycle in the rat (with a peak at estrus) and are positively regulated by a physiological doses of 17β-estradiol (Davies 2005).
To determine whether increased AnxA1 leads to increased AnxA1 action, anterior pituitary tissue from ovariectomised (low AnxA1) and 17β-estradiol-treated (high AnxA1) animals was exposed to forskolin and/or dexamethasone in vitro. The addition of 0.1 μM dexamethasone caused a greater inhibition of the forskolin-stimulated ACTH release in tissue with a high AnxA1 content compared to tissue with a low AnxA1 content. The effect of 17β-estradiol on externalization of AnxA1 from FS cells was investigated using a mouse FS cell line, TtT/GF cells. TtT/GF cells externalize Anx1 in response to dexamethasone. 17β-estradiol pretreatment (180 nMol, 24 h) increased the quantity of Anx1 externalized in response to 0.1 μMol dexamethasone. This effect of 17β-estradiol was abolished by the estrogen receptor inhibitor ICI182,780. Consistent with this, immunofluorescence studies showed both ERα and ERβ localized to the nucleus of TtT/GF cells.
These data suggest that the variation in anterior pituitary AnxA1 with the estrous cycle is due to the action of estradiol acting through nuclear estrogen receptors. The estradiol-stimulated increase in total pituitary AnxA1 is associated with an increased GF effect. Estradiol potentiation of GC-stimulated externalization of AnxA1 would also increase the GC effect. Together, these data are consistent with the hypothesis that cyclic variation in anterior pituitary AnxA1 is a component of the change in stress responsiveness during the estrous cycle.
01 - 05 Apr 2006
European Society of Endocrinology