title: Development by environment interactions controlling tryptophan hydroxylase expression.
abstract: 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.
authors.affiliation: Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, USA.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Hale
authors.forename: Anantha
authors.initials: A
authors.lastname: Shekhar
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lowry
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003863:Depression / Q000235:genetics / Q000523:psychology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D051379:Mice; D011903:Raphe Nuclei / Q000201:enzymology* / Q000254:growth & development; D051381:Rats; D012701:Serotonin / Q000096:biosynthesis* / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics; D013405:Suicide / Q000523:psychology; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D012701:Serotonin; C497467:TPH1 protein, human; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase; C504570:tph1 protein, rat; C504569:tph2 protein, rat