Marine Science Institute, University of Texas at Austin, Port Aransas, Texas 78373, USA.
J Toxicol Environ Health B Crit Rev. 2011;14(5-7):473-94. doi: 10.1080/10937404.2011.578563.
Tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin (5-HT) synthesis, performs an essential role in the maintenance of serotonergic functions in the central nervous system (CNS), including regulation of the neuroendocrine system controlling reproduction. The results of recent studies in a teleost model of neuroendocrine disruption, Atlantic croaker, indicated that hypothalamic TPH is a major site of interference of hypothalamic-pituitary-gonadal function by environmental stressors. The effects of exposure to two different types of environmental stressors, low dissolved oxygen (hypoxia) and a polychlorinated biphenyl mixture (Aroclor 1254), on the stimulatory brain serotonergic system controlling reproductive neuroendocrine function in Atlantic croaker are reviewed. Exposure to both stressors produced decreases in TPH activity, which were accompanied by a fall in hypothalamic 5-HT and gonadotropin-releasing hormone (GnRH I) content in the preoptic-anterior hypothalamic area and were associated with reduction in luteinizing hormone (LH) secretion and gonadal development. Pharmacological restoration of hypothalamic 5-HT levels after exposure to both stressors also restored neuroendocrine and reproductive functions, indicating that the serotonergic system is an important site for hypoxia- and Aroclor 1254-induced inhibition of reproductive neuroendocrine functions. The mechanisms underlying downregulation of TPH activity by these stressors remain unclear but may involve alterations in hypothalamic antioxidant status. In support of this hypothesis, treatment with an antioxidant, vitamin E, was found to reverse the inhibitory effects of Aroclor 1254 on TPH activity. The results suggest that TPH is a major target for neuroendocrine disruption by diverse environmental stressors.
色氨酸羟化酶（TPH）是 5-羟色胺（5-HT）合成的限速酶，在中枢神经系统（CNS）中 5-HT 能功能的维持中发挥着重要作用，包括对控制生殖的神经内分泌系统的调节。最近对一种神经内分泌干扰的硬骨鱼模型——大西洋月鱼的研究结果表明，下丘脑 TPH 是环境应激原干扰下丘脑-垂体-性腺功能的主要部位。本文综述了两种不同类型的环境应激原，低溶解氧（缺氧）和多氯联苯混合物（Aroclor 1254），对控制大西洋月鱼生殖神经内分泌功能的刺激脑 5-HT 能系统的影响。暴露于这两种应激原都会导致 TPH 活性降低，同时伴随着下丘脑 5-HT 和促性腺激素释放激素 I（GnRH I）含量下降，以及促黄体生成素（LH）分泌和性腺发育减少。暴露于这两种应激原后，用药物恢复下丘脑 5-HT 水平也恢复了神经内分泌和生殖功能，表明 5-HT 能系统是缺氧和 Aroclor 1254 抑制生殖神经内分泌功能的重要部位。这些应激原下调 TPH 活性的机制尚不清楚，但可能涉及下丘脑抗氧化状态的改变。支持这一假说，抗氧化剂维生素 E 的治疗发现可逆转 Aroclor 1254 对 TPH 活性的抑制作用。结果表明，TPH 是多种环境应激原引起的神经内分泌干扰的主要靶标。
