HPA axis changes during the initial phase of psychosocial stressor exposure in male mice.
HPA axis changes during the initial phase of psychosocial stressor exposure in male mice.
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DOI：
10.1530/joe-13-0027
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发表时间：
2013-08
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影响因子：
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通讯作者：
Nicole Uschold-Schmidt;D. Peterlik;A. Füchsl;S. Reber
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作者：
Nicole Uschold-Schmidt;D. Peterlik;A. Füchsl;S. Reber
慢性次级集落（CSC）住房19天的结果在基础上午皮质酮（CORT）水平不受影响，尽管肾上腺质量显着增加，可能是由肾上腺促肾上腺皮质激素（ACTH）的反应性减弱介导。考虑到基础早晨血浆CORT水平的显著增加早在CSC开始后48小时就恢复到基线水平，很可能在该初始阶段已经产生了减弱的ACTH反应性。本研究对此进行了测试。与先前的研究结果一致，CSC暴露10小时后，基础早晨血浆CORT水平升高，但不是48小时。基础早晨血浆ACTH浓度和相对在体内肾上腺皮质激素含量增加后10小时，并在较小程度上48小时的CSC曝光，正相关。在两个时间点后，响应于ACTH（100 nM）的相对体外肾上腺CORT分泌和11β-羟基类固醇脱氢酶2型（HSD 11B 2）的肾脏蛋白表达均未受影响。CSC暴露10 h后，关键类固醇生成酶的肾上腺mRNA表达未受影响/降低，暴露48 h后未受影响/升高。总之，我们的研究结果表明，在初始CSC阶段的基础血浆皮质功能亢进主要是由垂体ACTH释放的衰减。CSC暴露10小时后绝对肾上腺重量增加，但不是48小时，表明正常肾上腺质量的恢复也在较小程度上增加，以防止基础皮质功能亢进。酶促CORT降解和类固醇生成酶可用性的改变可能起作用，但必须在未来的研究中进一步解决。
Chronic subordinate colony (CSC) housing for 19 days results in unaffected basal morning corticosterone (CORT) levels despite a pronounced increase in adrenal mass, likely mediated by an attenuation of adrenal corticotropin (ACTH) responsiveness. Given that the pronounced increase in basal morning plasma CORT levels returns to baseline as early as 48 h after the start of CSC, it is likely that the attenuated ACTH responsiveness develops already during this initial phase. This was tested in the present study. In line with previous findings, basal morning plasma CORT levels were elevated following 10 h, but not 48 h, of CSC exposure. Basal morning plasma ACTH concentrations and relative in vivo adrenal CORT content were increased following 10 h and to a lesser extent following 48 h of CSC exposure, positively correlating. Relative in vitro adrenal CORT secretion in response to ACTH (100 nM) and kidney protein expression of 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) were unaffected following both time points. Adrenal mRNA expression of key steroidogenic enzymes was unaffected/decreased following 10 h and unaffected/increased following 48 h of CSC exposure. Together, our findings suggest that basal plasma hypercorticism during the initial CSC phase is mainly prevented by an attenuation of pituitary ACTH release. An increased absolute adrenal weight following 10 h, but not 48 h, of CSC exposure indicates that restoration of normal adrenal mass also adds to a lesser extent to prevent basal hypercorticism. A contributing role of alterations in enzymatic CORT degradation and steroidogenic enzyme availability is likely, but has to be further addressed in future studies.