Rapid non-genomic feedback effects of glucocorticoids on CRF-induced ACTH secretion in rats
Rapid non-genomic feedback effects of glucocorticoids on CRF-induced ACTH secretion in rats
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DOI：
10.1023/a:1026499604848
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发表时间：
2000-10-01
影响因子：
3.7
通讯作者：
Hirschelmann, R
中科院分区：
文献类型：
--
作者：
Hinz, B;Hirschelmann, R
目的。本研究探讨了皮质酮（皮质类固醇I型/ II型受体激动剂）和ru28362（皮质类固醇II型受体激动剂）对促肾上腺皮质激素释放因子（CRF）诱导的大鼠促肾上腺皮质激素（ACTH）分泌的快速负反馈作用。为了诱导快速反馈，在注射促垂体刺激CRF之前立即静脉注射糖皮质激素。5 ~ 30min后测定血浆ACTH水平，作为快速反馈的标志。类固醇给药后15分钟（皮质酮）和5分钟（RU 28362）对crf诱导的ACTH分泌的快速抑制作用明显。在其他皮质类固醇（皮质醇、地塞米松、醛固酮）存在时也观察到快速反馈抑制，而与结构无关的类固醇（β -雌二醇、黄体酮、canrenoate钾、alphaxalone）在这方面无活性。用皮质类固醇II型受体拮抗剂ru486或转录抑制剂放线菌素D对大鼠进行预处理后，快速反馈效应不变。我们的研究结果表明，糖皮质激素通过一种独立于糖皮质激素II型受体占据和mRNA从头合成的机制，在垂体水平上施加快速负反馈。总之，皮质激素特异性非基因组效应可能是促肾上腺皮质激素对促肾上腺皮质激素分泌的快速反应的基础。
Purpose. The present study investigates fast negative feedback actions of corticosterone (corticosteroid type I/type II receptor agonist) and RU 28362 (corticosteroid type II receptor agonist) on corticotropin-releasing factor (CRF)-induced adrenocorticotropic hormone (ACTH) secretion in rats.Methods. To induce fast feedback, glucocorticoids were administered intravenously immediately before injection of the hypophyseotropic stimulus CRF. Plasma ACTH levels, being determined 5 to 30 min thereafter, were used as markers of fast feedback.Results. Fast inhibitory effects on CRF-induced ACTH secretion became evident within 15 min (corticosterone) and 5 min (RU 28362) after steroid administration. Rapid feedback inhibition was also observed in the presence of other corticosteroids (cortisol, dexamethasone, aldosterone), whereas structurally-unrelated steroids (beta -estradiol, progesterone, potassium canrenoate, alphaxalone) were inactive in this respect. Pretreatment of rats with the corticosteroid type II receptor antagonist RU 486 or the transcription inhibitor actinomycin D left fast feedback effects unaltered.Conclusions. Our results demonstrate that glucocorticoids exert fast negative feedback at the pituitary level via a mechanism that is independent of corticosteroid type II receptor occupation and de novo synthesis of mRNA. In conclusion, corticosteroid-specific non-genomic effects may underly rapid glucocorticoid responses on CRF-induced ACTH secretion.