nnexin 1 (Anx 1) is a member of the annexin family of phospholipid- and calcium-binding proteins which has a well-demonstrated role in mediating the early delayed (30 min–3 h) inhibitory feedback effects of glucocorticoids in the pituitary. Anx 1 is located in folliculostellate (FS) cells and glucocorticoids act on these cells to externalise and stimulate the synthesis of Anx 1 which then acts on high affinity Anx 1-binding sites on the endocrine cells. The stress response is notably sexually dimorphic, with females being more susceptible except during pregnancy and lactation. We have examined the corticotrophs of the anterior pituitary in wild-type and Anx 1−/− animals to determine the effects of removal of Anx 1 in male and female mice. Our prediction was that the lack of inhibition would cause hyperactivity of the corticotrophs.
Anterior pituitary tissue was removed from Anx 1 +/+, +/− and −/− adult mice (n = 4 per group), fixed by immersion, and examined by confocal immunocytochemistry to determine the number of corticotrophs and by electron microscopy to examine the size, secretory granule population and secretory machinery of immunoidentified cells. Plasma corticosterone was measured by radioimmunoassay. No differences in any of the histological parameters could be detected in the female mice. By contrast in the male Anx 1 −/− mice there were approximately 3 times the number of corticotrophs as in the wild-type animals. However the corticotrophs in Anx 1 −/− mice were smaller (cytoplasm and nucleus) and had reduced numbers of secretory vesicles (the reduced number of vesicles parallelling the reduction in cell size). The amount of rough endoplasmic reticulum and Golgi was also reduced in the Anx 1 −/− male animals. In general data for the male Anx 1 +/− animals was intermediate between that of the wild-type and homozygotes. In female but not male Anx 1 −/− mice plasma corticosterone levels were increased compared to wild-type.
Many of these data were unexpected. One possible interpretation is that the Anx 1 −/− females are more resistant to glucocorticoid feedback at the pituitary than the males. The striking increase in the number of corticotrophs in the male Anx 1 −/− animals could suggest that, in males, a lack of glucocorticoid feedback via annexin has caused increased proliferation of the corticotrophs. However, in both cases the mechanism(s) remain to be determined.