Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, USA.
J Chem Neuroanat. 2011 Jul;41(4):219-26. doi: 10.1016/j.jchemneu.2011.05.002. Epub 2011 May 25.
Tryptophan hydroxylase is the rate-limiting enzyme in the biosynthesis of serotonin (5-hydroxytryptamine; 5-HT). Two isoforms of tryptophan hydroxylase, derived from different genes, tph1 and tph2, have been identified. The tph1 isoform is expressed in peripheral tissues, whereas tph2 is brain and neuron-specific. Recent studies suggest that tph2 expression and brain serotonin turnover are upregulated in depressed suicide patients, and drug-free depressed patients, respectively. Increased tph2 expression could result from genetic influences, early life developmental influences, adverse experience during adulthood, or interactions among these factors. Studies in rodents support the hypothesis that interactions between early life developmental influences and adverse experience during adulthood play an important role in determining tph2 expression. In this review, we highlight the evidence for the effects of adverse early life experience and stressful experience during adulthood on both tph1 and tph2 expression.
色氨酸羟化酶是 5-羟色胺（5-HT）生物合成中的限速酶。已经鉴定出两种色氨酸羟化酶同工酶，即源自不同基因的 tph1 和 tph2。tph1 同工酶在周围组织中表达，而 tph2 则是脑和神经元特异性的。最近的研究表明，在抑郁自杀患者和未经药物治疗的抑郁患者中，tph2 的表达和脑内 5-羟色胺周转率均升高。tph2 表达的增加可能是遗传影响、生命早期发育影响、成年期不良经历或这些因素相互作用的结果。啮齿动物研究支持这样一种假设，即生命早期发育影响和成年期不良经历之间的相互作用在决定 tph2 表达方面起着重要作用。在这篇综述中，我们强调了不良的生命早期经历和成年期应激经历对 tph1 和 tph2 表达的影响。
