John C D, Theogaraj E, Christian H C, Morris J F, Smith S F, Buckingham J C
Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Imperial College London, Hammersmith Campus, London, UK.
J Neuroendocrinol. 2006 Dec;18(12):949-59. doi: 10.1111/j.1365-2826.2006.01493.x.
Perinatal glucocorticoid (GC) treatment is increasingly associated with long-term disturbances in hypothalamo-pituitary-adrenocortical function. In the male rat, such treatment induces profound molecular, morphological and functional changes in the anterior pituitary gland at adulthood. To determine whether these effects are sex-specific, we have examined the effects of perinatal dexamethasone treatment on the female pituitary gland, focusing on (i) the integrity of the annexin 1 (ANXA1) dependent regulatory effects of GCs on adrenocorticotrophic hormone (ACTH) release and (ii) corticotroph and folliculo-stellate (FS) cell morphology. Dexamethasone was given to pregnant (gestational days 16-19) or lactating (days 1-7 post partum) rats via the drinking water (1 microg/ml); controls received normal drinking water. Pituitary tissue from the female offspring was examined ex vivo at adulthood (60-90 days). Both treatment regimes reduced the intracellular and cell surface ANXA1 expression, as determined by western blot analysis and quantitative immunogold electron microscopic histochemistry. In addition, they compromised the ability of dexamethasone to suppress the evoked release of ACTH from the excised tissue in vitro, a process which requires the translocation of ANXA1 from the cytoplasm to the cell surface of FS cells. Although neither treatment regime affected the number of FS cells or corticotrophs, both altered the subcellular morphology of these cells. Thus, prenatal dexamethasone treatment increased while neonatal treatment decreased FS cell size and cytoplasmic area. By contrast, corticotroph size was unaffected by either treatment, as also was the size of the secretory granules. Corticotroph granule density and margination were, however, increased markedly by the prenatal treatment, while the neonatal treatment had no effect on granule density but decreased granule margination. Thus, perinatal dexamethasone treatment exerts long-term effects on the female pituitary gland, altering gene expression, cell morphology and the ANXA1-dependent GC regulation of ACTH secretion. The changes are similar but not identical to those reported in the male.
围产期糖皮质激素（GC）治疗与下丘脑 - 垂体 - 肾上腺皮质功能的长期紊乱越来越相关。在雄性大鼠中，这种治疗会在成年期引起垂体前叶深刻的分子、形态和功能变化。为了确定这些影响是否具有性别特异性，我们研究了围产期地塞米松治疗对雌性垂体的影响，重点关注（i）糖皮质激素对促肾上腺皮质激素（ACTH）释放的膜联蛋白1（ANXA1）依赖性调节作用的完整性，以及（ii）促肾上腺皮质激素细胞和滤泡 - 星状（FS）细胞的形态。通过饮用水（1微克/毫升）给怀孕（妊娠第16 - 19天）或哺乳期（产后第1 - 7天）的大鼠给予地塞米松；对照组给予正常饮用水。成年期（60 - 90天）对雌性后代的垂体组织进行离体检查。通过蛋白质印迹分析和定量免疫金电子显微镜组织化学测定，两种治疗方案均降低了细胞内和细胞表面的ANXA1表达。此外，它们损害了地塞米松在体外抑制从切除组织中诱发的ACTH释放的能力，这一过程需要ANXA1从细胞质转运到FS细胞的细胞表面。虽然两种治疗方案均未影响FS细胞或促肾上腺皮质激素细胞的数量，但都改变了这些细胞的亚细胞形态。因此，产前地塞米松治疗增加了而新生儿期治疗降低了FS细胞大小和细胞质面积。相比之下，促肾上腺皮质激素细胞大小不受任何一种治疗的影响，分泌颗粒大小也是如此。然而，产前治疗显著增加了促肾上腺皮质激素细胞颗粒密度和边缘化，而新生儿期治疗对颗粒密度没有影响，但降低了颗粒边缘化。因此，围产期地塞米松治疗对雌性垂体产生长期影响，改变基因表达、细胞形态以及ANXA1依赖性糖皮质激素对ACTH分泌的调节。这些变化与在雄性中报道的相似但不完全相同。
