Morris J F, Omer S, Davies E, Wang E, John C, Afzal T, Wain S, Buckingham J C, Flower R J, Christian H C
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
J Neuroendocrinol. 2006 Nov;18(11):835-46. doi: 10.1111/j.1365-2826.2006.01481.x.
Annexin 1 (ANXA1) is a member of the annexin family of phospholipid- and calcium-binding proteins with a well demonstrated role in early delayed (30 min to 3 h) inhibitory feedback of glucocorticoids in the pituitary. We have examined corticotrophs in wild-type and ANXA1 knockout mice to determine the effects of lack of ANXA1 in male and female animals. Anterior pituitary tissue from ANXA1 wild-type, heterozygote and null mice was fixed and examined (i) by confocal immunocytochemistry to determine the number of corticotrophs and (ii) by electron microscopy to examine the size, secretory granule population and secretory machinery of corticotrophs. No differences in these parameters were detected in female mice. In male ANXA1 null mice, there were approximately four-fold more corticotrophs than in wild-type animals. However, the corticotrophs in ANXA1 null mice were smaller and had reduced numbers of secretory granules (the reduction in granules paralleled the reduction in cell size). No differences in the numerical density of folliculo-stellate, gonadotroph, lactotroph or somatotroph cells were detected in male ANXA1 null mice. Plasma corticosterone, adrenocorticotrophic hormone (ACTH) and pituitary pro-opiomelanocortin mRNA were unchanged but pituitary ACTH content was increased in male ANXA1 null mice. Interleukin (IL)-6 pituitary content was significantly elevated in male and reduced in female ANXA1 null mice compared to wild-type. In conclusion, these data indicate that ANXA1 deficiency is associated with gender-specific changes in corticotroph number and structure, via direct actions of ANXA1 and/or indirect changes in factors such as IL-6.
膜联蛋白1（ANXA1）是膜联蛋白家族中一种结合磷脂和钙的蛋白质，在垂体中糖皮质激素的早期延迟（30分钟至3小时）抑制性反馈中发挥着明确作用。我们检测了野生型和ANXA1基因敲除小鼠的促肾上腺皮质激素细胞，以确定ANXA1缺失对雄性和雌性动物的影响。对ANXA1野生型、杂合子和基因敲除小鼠的垂体前叶组织进行固定并检查：（i）通过共聚焦免疫细胞化学确定促肾上腺皮质激素细胞的数量；（ii）通过电子显微镜检查促肾上腺皮质激素细胞的大小、分泌颗粒数量和分泌机制。在雌性小鼠中未检测到这些参数的差异。在雄性ANXA1基因敲除小鼠中，促肾上腺皮质激素细胞数量比野生型动物多约四倍。然而，ANXA1基因敲除小鼠中的促肾上腺皮质激素细胞较小，分泌颗粒数量减少（颗粒减少与细胞大小减少平行）。在雄性ANXA1基因敲除小鼠中，未检测到滤泡星状细胞、促性腺激素细胞、催乳素细胞或生长激素细胞的数量密度差异。雄性ANXA1基因敲除小鼠的血浆皮质酮、促肾上腺皮质激素（ACTH）和垂体阿黑皮素原mRNA未发生变化，但垂体ACTH含量增加。与野生型相比，雄性ANXA1基因敲除小鼠的垂体白细胞介素（IL）-6含量显著升高，而雌性则降低。总之，这些数据表明，ANXA1缺乏与促肾上腺皮质激素细胞数量和结构的性别特异性变化有关，这是通过ANXA1的直接作用和/或IL-6等因子的间接变化实现的。
