The rapid release of corticosterone from the adrenal induced by ACTH is mediated by nitric oxide acting by prostaglandin E2
The rapid release of corticosterone from the adrenal induced by ACTH is mediated by nitric oxide acting by prostaglandin E2
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DOI：
10.1073/pnas.0502136102
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发表时间：
2005-04-26
影响因子：
11.1
通讯作者：
Rettori, V
中科院分区：
文献类型：
--
作者：
Mohn, CE;Fernandez-Solari, J;Rettori, V
肾上腺皮质是哺乳动物的主要应激器官，对多种外部和内部应激源反应迅速。促肾上腺皮质激素(ACTH)是肾上腺皮质的主要刺激物，激活皮质类固醇的合成和分泌。我们评价了ACTH对雄性大鼠肾上腺的作用机制，并在体外保留了腺体的结构。我们证明了一氧化氮供体硝普钠(NIP)和ACTH都能刺激皮质酮的释放。NO介导了ACTH的急性反应，因为NO合成酶抑制剂N omega-硝基-L-精氨酸甲酯和NO清除剂血红蛋白阻断了ACTH诱导的皮质酮释放的刺激。NP刺激前列腺素E的释放，进而刺激肾上腺皮质酮的释放。此外，吲哚美辛抑制环氧合酶，从而抑制前列腺素释放，阻止由NP和ACTH诱导的肾上腺皮质酮释放，表明前列腺素介导了急性皮质酮释放。与ACTH或NP孵育后，肾上腺中皮质酮的含量低于对照组，表明在此期间皮质酮的从头合成不足以跟上储存的激素的释放。与在缓冲液中孵育的腺体相比，ACTH或NP诱导的释放耗尽了肾上腺皮质酮含量约40%。其快速释放的机制是：ACTH激活NO合成酶产生的NO激活环氧合酶，产生PGE(2)，PGE(2)进而释放储存在微囊和其他细胞器中的皮质酮。
The adrenal cortex is a major stress organ in mammals that reacts rapidly to a multitude of external and internal stressors. Adrenocorticotropin (ACTH) is the main stimulator of the adrenal cortex, activating corticosteroid synthesis and secretion. We evaluated the mechanism of action of ACTH on adrenals of male rats, preserving the architecture of the gland in vitro. We demonstrated that both sodium nitroprusside (NIP), a nitric oxide (NO) donor, and ACTH stimulate corticosterone release. NO mediated the acute response to ACTH because N omega-nitro-L-arginine methyl ester, a NO synthase inhibitor, and hemoglobin, a NO scavenger, blocked the stimulation of corticosterone release induced by ACTH. NP stimulated prostaglandin E release, which in turn stimulated corticosterone release from the adrenal. Additionally, indomethacin, which inhibits cyclooxygenase, and thereby, prostaglandin release, prevented corticosterone release from the adrenal induced by both NP and ACTH, demonstrating that Prostaglandins mediate acute corticosterone release. Corticosterone content in adrenals after incubation with ACTH or NP was lower than in control glands, indicating that any de novo synthesis of corticosterone during this period was not sufficient to keep up with the release of the stored hormone. The release induced by ACTH or NP depleted the corticosterone content in the adrenal by approximate to 40% compared with the content of glands incubated in buffer. The mechanism of rapid release is as follows: NO produced by NO synthase activation by ACTH activates cyclooxygenase, which generates PGE(2), which in turn releases corticosterone stored in microvesicles and other organelles.