Perras B, Berkemeier E, Rasch B, Fehm H L, Born J
Department of Neuroendocrinology, University of Lübeck, Germany.
Neuropeptides. 2007 Aug;41(4):233-8. doi: 10.1016/j.npep.2007.03.002. Epub 2007 May 7.
Non-glucocorticoid inhibitors of the HPA-system are of utmost interest in the treatment of diseases with impaired regulation of this system, like the metabolic syndrome and depression. In rats, a fragment of the thyreotropin-releasing hormone (TRH) preprohormone, preproTRH((178-199)), has been demonstrated to inhibit basal and stimulated secretion of cortisol. Our pilot study aimed to explore the first time similar effects of the homologue peptide preproTRH((158-183)) in healthy humans. In a double-blind within-subject comparison, eight healthy young men were infused intravenously with placebo and preproTRH((158-183)) at varying doses of 5, 10, 25 and 50 mg/kg of body weight. After 15 min of infusion a corticotropin-releasing hormone (CRH)/vasopressin-test was performed. Plasma concentrations of pituitary hormones and free thyroxine, blood pressure, heart rate and feelings of activation and mood were assessed repeatedly at close intervals. Individual hormone profiles and collapsed data across all doses did not reveal any effects of preproTRH((158-183)) on HPA-activity, although it increased TSH and fT4, stimulated the release of GH and increased systolic blood pressure in the course of the experiment (p<0.05, for all effects). Self-reports indicated enhanced feelings of activation and general well-being following preproTRH (p<0.05). Our data exclude a substantial inhibitory effect of preproTRH((158-183)) on HPA secretory activity and, thus, contrast with findings in rats. In humans, the peptide appears to even exert an albeit weak stimulatory effect on autonomic stress systems as indicated by increased cardiovascular activity in combination with enhanced subjective arousal.
下丘脑-垂体-肾上腺（HPA）系统的非糖皮质激素抑制剂在治疗该系统调节受损的疾病（如代谢综合征和抑郁症）方面具有极大的研究价值。在大鼠中，促甲状腺激素释放激素（TRH）前体激素的一个片段，即前proTRH((178 - 199))，已被证明可抑制皮质醇的基础分泌和刺激分泌。我们的初步研究旨在首次探索同源肽前proTRH((158 - 183))在健康人类中的类似作用。在一项双盲自身对照比较中，八名健康年轻男性被静脉输注不同剂量（5、10、25和50毫克/千克体重）的安慰剂和前proTRH((158 - 183))。输注15分钟后进行促肾上腺皮质激素释放激素（CRH）/血管加压素试验。在短时间内反复评估垂体激素、游离甲状腺素的血浆浓度、血压、心率以及激活感和情绪。尽管在实验过程中前proTRH((158 - 183))增加了促甲状腺激素（TSH）和游离甲状腺素（fT4），刺激了生长激素（GH）的释放并升高了收缩压（所有效应p<0.05），但个体激素谱和所有剂量的汇总数据均未显示前proTRH((158 - 183))对HPA活性有任何影响。自我报告表明，输注前proTRH后激活感和总体幸福感增强（p<0.05）。我们的数据排除了前proTRH((158 - 183))对HPA分泌活性的显著抑制作用，因此与大鼠的研究结果形成对比。在人类中，该肽似乎甚至对自主应激系统产生了微弱的刺激作用，这表现为心血管活动增加以及主观唤醒增强。
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