Differential glucocorticoid effects on stress-induced gene expression in the paraventricular nucleus of the hypothalamus and ACTH secretion in the rat.
Differential glucocorticoid effects on stress-induced gene expression in the paraventricular nucleus of the hypothalamus and ACTH secretion in the rat.
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DOI：
10.1080/10253890802530730
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发表时间：
2009-09
期刊：
影响因子：
--
通讯作者：
Spencer RL
中科院分区：
文献类型：
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作者：
Pace TW;Gaylord RI;Jarvis E;Girotti M;Spencer RL
尽管以前的研究已经研究了促肾上腺皮质激素（ACTH）分泌在多大程度上依赖于内源性糖皮质激素水平，但很少有人研究了包含下丘脑室旁核（PVN）亚区域的促肾上腺皮质激素释放激素（CRH）神经元内基因表达的平行糖皮质激素依赖性。这项研究检查了肾上腺切除 (ADX) 大鼠 PVN 中三种立即早期基因（c-fos、zif268 和 NGFI-B mRNA）和两种表型限制性立即早期基因（编码 ACTH 促分泌素（CRH 和精氨酸加压素 [AVP] hnRNA））在静息和应激诱导下的表达，这些大鼠给予肾上腺切除 (ADX) 大鼠 5 天饮用 0.9% 盐水或饮用盐水 皮质酮（CORT；25 µg/ml）。测试前 18 小时用生理盐水替换含 CORT 的生理盐水，以确保测试时 CORT 的清除。 30 分钟约束后 0、15、30、60 或 120 分钟检查相关措施。与假手术相比，ADX 产生了基础 ACTH 分泌的大量上调，但只有基础 PVN CRH 和小细胞 (mp) PVN AVP hnRNA 表达增加的趋势，以及抑制诱导的 ACTH 分泌和所检查的所有五个基因表达的显着增加。含有盐水的 CORT 在 ADX 大鼠的 PVN 中部分正常化基础和抑制诱导的 ACTH 分泌以及抑制诱导的 AVP hnRNA、c-fos mRNA 和 zif268 mRNA。相反，在有或没有 CORT 替代的 ADX 大鼠之间，约束诱导的 PVN CRH hnRNA 和 NGFI-B mRNA 的表达模式没有差异。鉴于在任何一组 ADX 大鼠中进行约束挑战时均不存在循环 CORT，因此 CORT 替代对约束诱导的 PVN 基因表达的差异影响必须反映 PVN 中这些基因的表达对先前存在的 CORT 的差异依赖性。
Although previous studies have examined the extent to which adrenocorticotropic hormone (ACTH) secretion depends on endogenous glucocorticoid levels, few have examined the parallel glucocorticoid dependency of gene expression within the corticotropin releasing hormone (CRH) neuron containing subregion of the hypothalamic paraventricular nucleus (PVN). This study examined resting and stress-induced expression of three immediate early genes (c-fos, zif268, and NGFI-B mRNAs) and two phenotypic restricted immediate early genes that code for ACTH secretagogues (CRH and arginine vasopressin [AVP] hnRNAs) in the PVN of adrenalectomized (ADX) rats given either 0.9% saline to drink for 5 days or saline with corticosterone (CORT; 25 µg/ml). CORT-containing saline was replaced with saline 18 h before testing to ensure clearance of CORT at the time of testing. Dependent measures were examined 0, 15, 30, 60, or 120 min after 30 min restraint. Compared to sham surgery, ADX produced a large upregulation of basal ACTH secretion but only a trend for an increase in basal PVN CRH and parvocellular (mp) PVN AVP hnRNA expression, and a marked augmentation of restraint-induced ACTH secretion and the expression of all five genes examined. CORT containing saline partially normalized basal and restraint-induced ACTH secretion and restraint-induced AVP hnRNA, c-fos mRNA, and zif268 mRNA in the PVN in ADX rats. In contrast, expression patterns of restraint-induced PVN CRH hnRNA and NGFI-B mRNA were not different between ADX rats with or without CORT replacement. Given that there was no circulating CORT present at the time of restraint challenge in either group of ADX rats, the differential impact of CORT replacement on restraint-induced PVN gene expression must reflect differential dependency of the expression of these genes in the PVN on the prior presence of CORT.