Lai Guey-Jen, McCobb David P
Department of Neurobiology and Behavior, Cornell University, Ithaca, New York 14853, USA.
Endocrinology. 2006 Aug;147(8):3961-7. doi: 10.1210/en.2005-1551. Epub 2006 May 4.
Stress triggers release of ACTH from the pituitary, glucocorticoids from the adrenal cortex, and epinephrine from the adrenal medulla. Although functions differ, these hormone systems interact in many ways. Previous evidence indicates that pituitary and steroid hormones regulate alternative splicing of the Slo gene at the stress axis-regulated exon (STREX), with functional implications for the calcium-activated K+ channels prominent in adrenal medullary and pituitary cells. Here we examine the role of corticosterone in Slo splicing regulation in pituitary and adrenal tissues during the stress-hyporesponsive period of early rat postnatal life. The sharp drop in plasma corticosterone (CORT) that defines this period offers a unique opportunity to test CORT's role in Slo splicing. We report that in both adrenal and pituitary tissues, the percentage of Slo transcripts having STREX declines and recovers in parallel with CORT. Moreover, addition of 500 nm CORT to cultures of anterior pituitary cells from 13-, 21-, and 30-d postnatal animals increased the percentage of Slo transcripts with STREX, whereas 20 microm CORT reduced STREX representation. Applied to adrenal chromaffin cells, 20 microm CORT decreased STREX inclusion, whereas neither 500 nm nor 2 microm had any effect. The mineralocorticoid receptor antagonist RU28318 abolished the effect of 500 nm CORT on splicing in pituitary cells, whereas the glucocorticoid receptor antagonist RU38486 blocked the effect of 20 microm CORT on adrenal chromaffin cells. These results support the hypothesis that the abrupt, transient drop in CORT during the stress-hyporesponsive period drives the transient decline in STREX splice variant representation in pituitary, but not adrenal.
应激会触发垂体释放促肾上腺皮质激素（ACTH）、肾上腺皮质释放糖皮质激素以及肾上腺髓质释放肾上腺素。尽管这些激素系统的功能各不相同，但它们在许多方面相互作用。先前的证据表明，垂体激素和类固醇激素在应激轴调节外显子（STREX）处调节Slo基因的可变剪接，这对肾上腺髓质和垂体细胞中突出的钙激活钾通道具有功能影响。在此，我们研究了在大鼠出生后早期应激低反应期，皮质酮在垂体和肾上腺组织中Slo剪接调节中的作用。定义这一时期的血浆皮质酮（CORT）的急剧下降为测试CORT在Slo剪接中的作用提供了独特的机会。我们报告，在肾上腺和垂体组织中，具有STREX的Slo转录本的百分比与CORT平行下降和恢复。此外，向出生后13天、21天和30天动物的垂体前叶细胞培养物中添加500 nM CORT会增加具有STREX的Slo转录本的百分比，而20 μM CORT会降低STREX的比例。应用于肾上腺嗜铬细胞时，20 μM CORT会降低STREX的包含率，而500 nM和2 μM均无任何影响。盐皮质激素受体拮抗剂RU28318消除了500 nM CORT对垂体细胞剪接的影响，而糖皮质激素受体拮抗剂RU38486则阻断了20 μM CORT对肾上腺嗜铬细胞的影响。这些结果支持了这样一种假设，即在应激低反应期CORT的突然、短暂下降驱动了垂体而非肾上腺中STREX剪接变体比例的短暂下降。
