Cremades A, Peñafiel R, Rausell V, Del Rio-Garcia J, Smyth D G
Department of Physiology and Pharmacology, University of Murcia, Spain.
Eur J Pharmacol. 1998 Sep 25;358(1):63-7. doi: 10.1016/s0014-2999(98)00593-7.
Three naturally occurring peptides, pGlu-Glu-Pro amide, pGlu-Phe-Pro amide and pGlu-Gln-Pro amide, with similar structures to thyrotropin releasing hormone (TRH) have recently been identified but no studies of their in vivo activities have been reported previously. We describe here the ability of pGlu-Phe-Pro amide and pGlu-Glu-Pro amide to influence thyroid status. Subcutaneous administration of these 'TRH-like' peptides in male and female CDI mice led to increased levels of triiodothyronine (T3) and to a lesser extent tetraiodothyronine (T4) in the circulation. pGlu-Phe-Pro amide was more potent than pGlu-Glu-Pro amide; it exhibited a similar potency to pGlu-His-Pro amide (TRH). pGlu-Phe-Pro amide, pGlu-Glu-Pro amide and TRH produced significantly greater effects in the female than in the male. Castration of male mice led to increased activities, with potencies comparable to those seen in the female; in contrast treatment of female mice with testosterone resulted in reduced activities, similar to those observed in the control male. The effects of potassium deprivation on the activities of the TRH-like peptides were also investigated. This diet, which results in decreased testosterone levels in the male, led to increased activities of the TRH-like peptides and TRH, approaching the potencies observed in the female. The results demonstrate that the TRH-like peptides pGlu-Phe-Pro amide and pGlu-Glu-Pro amide which occur naturally in the thyroid gland exhibit biological activity in influencing thyroid status in vivo. The activities are sensitive to testosterone.
最近已鉴定出三种天然存在的肽，即焦谷氨酸-谷氨酸-脯氨酰胺、焦谷氨酸-苯丙氨酸-脯氨酰胺和焦谷氨酸-谷氨酰胺-脯氨酰胺，它们的结构与促甲状腺激素释放激素（TRH）相似，但此前尚未有关于它们体内活性的研究报道。我们在此描述了焦谷氨酸-苯丙氨酸-脯氨酰胺和焦谷氨酸-谷氨酸-脯氨酰胺影响甲状腺状态的能力。在雄性和雌性CDI小鼠中皮下注射这些“TRH样”肽，导致循环中三碘甲状腺原氨酸（T3）水平升高，四碘甲状腺原氨酸（T4）水平在较小程度上也有所升高。焦谷氨酸-苯丙氨酸-脯氨酰胺比焦谷氨酸-谷氨酸-脯氨酰胺更有效；它表现出与焦谷氨酸-组氨酸-脯氨酰胺（TRH）相似的效力。焦谷氨酸-苯丙氨酸-脯氨酰胺、焦谷氨酸-谷氨酸-脯氨酰胺和TRH对雌性的作用明显大于对雄性的作用。阉割雄性小鼠导致活性增加，效力与雌性小鼠相当；相反，用睾酮处理雌性小鼠导致活性降低，与对照雄性小鼠中观察到的相似。还研究了钾缺乏对TRH样肽活性的影响。这种饮食会导致雄性小鼠睾酮水平降低，从而导致TRH样肽和TRH的活性增加，接近在雌性小鼠中观察到的效力。结果表明，甲状腺中天然存在的TRH样肽焦谷氨酸-苯丙氨酸-脯氨酰胺和焦谷氨酸-谷氨酸-脯氨酰胺在体内影响甲状腺状态时表现出生物活性。这些活性对睾酮敏感。
