Goya R G, Brown O A, Bolognani F
INIBIOLP-Histology B, Faculty of Medicine, National University of La Plata, Argentina.
Neuroimmunomodulation. 1999 Jan-Apr;6(1-2):137-42. doi: 10.1159/000026373.
The pituitary-thymic axis constitutes a bidirectional circuit where the ascending feedback loop is effected by thymic factors of epithelial origin. The aim of the present article is to review the evidence demonstrating that aging brings about a progressive disruption in the integration of this network. In doing so, we briefly review the experimental evidence supporting the view that immune and neuroendocrine aging are interdependent processes. The advantages and limits of the nude mouse as a model of thymus-dependent accelerated aging is also discussed. Next, we review a number of studies which show that the endocrine thymus produces several bioactive molecules, generally called thymic hormones, which in addition to possessing immunoregulatory properties are also active on nervous and endocrine circuits. In particular, the reported activities of thymosin fraction 5 (TF5), thymosin alpha-1 and thymosin beta-4 on beta-endorphin, ACTH, glucocorticoids, LHRH and LH secretion in different animal and cell models are reviewed. The known hypophysiotropic actions of other thymic hormones like thymulin, homeostatic thymus hormone (HTH) and thymus factor are summarized. Aging has a significant impact on pituitary responsiveness to thymic hormones. Thus, it has been reported that TF5 and HTH have thyrotropin-inhibiting activity in young but not in old rats. Furthermore, intravenous administration of HTH was also able to reduce plasma GH and increase corticosterone levels in both young and old rats, although these responses were much weaker in the old animals. Further evidence on this topic is discussed. It is proposed that in addition to its central role in the regulation of the immune function, the thymus gland may extend its influence to nonimmunologic components of the body, including the neuroendocrine system. The early onset of thymus involution might therefore act as a triggering event which would initiate the gradual decline in homeostatic potential that characterizes the aging process.
垂体 - 胸腺轴构成一个双向回路，其中上行反馈回路由上皮来源的胸腺因子介导。本文旨在综述相关证据，以证明衰老会导致该网络整合的逐渐破坏。在此过程中，我们简要回顾支持免疫衰老和神经内分泌衰老相互依存观点的实验证据。还讨论了裸鼠作为胸腺依赖型加速衰老模型的优势和局限性。接下来，我们综述了多项研究，这些研究表明内分泌胸腺会产生几种生物活性分子，通常称为胸腺激素，它们除了具有免疫调节特性外，对神经和内分泌回路也有活性。特别回顾了在不同动物和细胞模型中，胸腺素组分5（TF5）、胸腺素α-1和胸腺素β-4对β-内啡肽、促肾上腺皮质激素、糖皮质激素、促性腺激素释放激素和促黄体生成素分泌的已知活性。总结了其他胸腺激素如胸腺生成素、稳态胸腺激素（HTH）和胸腺因子已知的促垂体作用。衰老对垂体对胸腺激素的反应性有显著影响。因此，据报道TF5和HTH在年轻大鼠中有促甲状腺素抑制活性，而在老年大鼠中则没有。此外，静脉注射HTH也能够降低年轻和老年大鼠的血浆生长激素水平并提高皮质酮水平，尽管老年动物的这些反应要弱得多。还讨论了关于该主题的更多证据。有人提出，胸腺除了在免疫功能调节中起核心作用外，可能还会将其影响扩展到身体的非免疫成分，包括神经内分泌系统。胸腺退化的早期发生可能因此成为一个触发事件，引发稳态潜能的逐渐下降，这是衰老过程的特征。
