Endocrine Abstracts (2006) 11 P576

Structural analysis of somatotrophs and lactotrophs in annexin 1 null mice

T Afzal1, JF Morris1, JC Buckingham2 & HC Christian1

1University of Oxford, Oxford, Oxon, United Kingdom; 2Imperial College, London, United Kingdom.

Annexin 1 (ANXA1) is a member of the annexin family of phospholipid- and calcium- binding proteins with a well-demonstrated role in the inhibitory actions of glucocorticoids on the release of ACTH, TSH, GH and PRL from the anterior pituitary. Consistent with these findings plasma PRL content is raised in male ANXA1 null mice vs wild-type controls (Cover et al Endocrine Abstracts 8, P69). Here we test the hypothesis that because ANXA1 mediates some of the inhibitory actions of glucocorticoids on GH and PRL secretion the somatotrophs and lactotrophs in ANXA1 null mice would be more active. Anterior pituitary tissue from male ANXA1 wild-type and null adult mice (n=6 of each) was fixed, examined by immunocytochemistry to determine the number of somatotrophs and lactotrophs, and by electron microscopy to examine the size, secretory granule population and secretory machinery of somatotrophs and lactotrophs. No significant differences in lactotroph or somatotroph number, cell size and density of secretory granules were measured. However, ANXA1 null somatotrophs and lactotrophs demonstrated significantly (P<0.05) increased margination of secretory granules to the plasma membrane and increased (P<0.05) amounts of rough endoplasmic reticulum (ER). Secretory granule diameter was significantly increased (P<0.05) in somatotrophs. Although cell size and amount of secretory granules were unchanged, more rough ER and increased granule margination to the plasma membrane suggest that in the absence of ANXA1 the lactotrophs and somatotrophs are more active. Although ANXA1 has a role in exerting anti-proliferative actions of glucocorticoids it does not appear to regulate lactotroph or somatotroph cell number. These data are consistent with our hypothesis that in ANXA1 null animals there is a reduction in the annexin mediated glucocorticoid inhibition of hormone release from somatotrophs and lactotrophs.

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