Endocrine Abstracts (2004) 7 OC2

Gonadotrophs in annexin 1 knockout mice demonstrate enhanced secretory activity by structural analysis

S Wain1, JF Morris1, JC Buckingham2 & HC Christian1

1Department of Human Anatomy and Genetics, University of Oxford, Oxford, UK; 2Department of Neuroendocrinology, Imperial College, London, UK.

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. ANXA1 and ANXA1 truncated peptides have also recently been found to mimic glucocorticoid suppression of LH release (John et al, 2003 J Neuroendocrinol 15, 946-57). Here we test the hypothesis that because ANXA1 mediates some of the inhibitory actions of glucocorticoids the gonadotrophs in ANXA1 -/- mice would be more active.

Anterior pituitary tissue from male and female ANXA1 +/+, +/- and -/- adult mice (n=4 of each) was fixed, examined by immunocytochemistry to determine the number of gonadotrophs, and by electron microscopy to examine the size, secretory granule population and secretory machinery of gonadotrophs. No significant differences in gonadotroph number or cell size were measured. Howe- mice had significantly (P<0.01) reduced numbers of secretory/- mice had significantly (P<0.01) reduced numbers of secretory granules, secretory granule size was reduced (P<0.05), and there was increased margination of the granules to the plasma membrane (P<0.05). The amount of rough endoplasmic reticulum (ER) was significantly increased (P<0.01). In general, data for +/- was intermediate between that of wild type and homozygotes. No gender differences in phenotype were observed.

These data suggest that in the absence of ANXA1 there is an increase in secretory granule turnover (indicated by the smaller granule size) and the gonadotrophs are significantly more active (as shown by more rough ER and increased granule margination). Such changes are consistent with our hypothesis that in ANXA1 -/- animals there is a reduction in the annexin mediated glucocorticoid inhibition of hormone release from gonadotrophs.

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