ReviewAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics2012
Advances in tryptophan hydroxylase-2 gene expression regulation: new insights into serotonin-stress interaction and clinical implications.
Review in American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 95 citations in OpenAlex.
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- Histone deacetylase SIRT6 regulates tryptophan catabolism and prevents metabolite imbalance associated with neurodegeneration.Nature communications · 2025Article
- Influence of TPH2 DNA methylation and family functioning, parenting styles on OCD severity.BMC psychiatry · 2025Article
- Parallel Gene Expression Changes in Ventral Midbrain Dopamine and GABA Neurons during Normal Aging.eNeuro · 2025Article
- Phytochemicals Modulate Biosynthesis and Function of Serotonin, Dopamine, and Norepinephrine for Treatment of Monoamine Neurotransmission-Related Psychiatric Diseases.International journal of molecular sciences · 2025Review
- Dysregulation of Retinal Melatonin Biosynthetic Pathway and Differential Expression of Retina-Specific Genes Following Blast-Induced Ocular Injury in Ferrets.Neurology international · 2025Article
- Enduring Neurobiological Consequences of Early-Life Stress: Insights from Rodent Behavioral Paradigms.Biomedicines · 2024Review
- Behavioural and physiological responses to stressors in sheep with temperament classified by genotype or phenotype.Scientific reports · 2024Article
- Trace amine-associated receptor 1 agonist reduces aggression in brain serotonin-deficient tryptophan hydroxylase 2 knockout rats.Frontiers in psychiatry · 2024Article
- D-mannose is a rapid inducer of ACSS2 to trigger rapid and long-lasting antidepressant responses through augmenting BDNF and TPH2 levels.Translational psychiatry · 2023Article
- Polymorphisms in genes of melatonin biosynthesis and signaling support the light-at-night hypothesis for breast cancer.European journal of epidemiology · 2023Article
- Peripheral Serotonin Deficiency Affects Anxiety-like Behavior and the Molecular Response to an Acute Challenge in Rats.International journal of molecular sciences · 2022Article
- Monoaminergic Multilocus Genetic Variants Interact with Stressful Life Events in Predicting Changes in Adolescent Anxiety Symptoms: A One-year Longitudinal Study.Journal of youth and adolescence · 2021Article
- Neonatal Serotonin Depletion Induces Hyperactivity and Anxiolytic-like Sex-Dependent Effects in Adult Rats.Molecular neurobiology · 2021Article
- A Systems Biology Approach to Investigating the Interaction between Serotonin Synthesis by Tryptophan Hydroxylase and the Metabolic Homeostasis.International journal of molecular sciences · 2021Article
- Pomegranate derivative urolithin A enhances vitamin D receptor signaling to amplify serotonin-related gene induction by 1,25-dihydroxyvitamin D.Biochemistry and biophysics reports · 2020Article
- Effects ofJournal of neurology, neurosurgery, and psychiatry · 2020Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Serotonin (5-HT) modulates the stress response by interacting with the hormonal hypothalamic-pituitary-adrenal (HPA) axis and neuronal sympathetic nervous system (SNS). Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in 5-HT biosynthesis, and the recent identification of a second, neuron-specific TPH isoform (TPH2) opened up a new area of research. While TPH2 genetic variance has been linked to numerous behavioral traits and disorders, findings on TPH2 gene expression have not only reinforced, but also provided new insights into, the long-recognized but not yet fully understood 5-HT-stress interaction. In this review, we summarize advances in TPH2 expression regulation and its relevance to the stress response and clinical implications. Particularly, based on findings on rhesus monkey TPH2 genetics and other relevant literature, we propose that: (i) upon activation of adrenal cortisol secretion, the cortisol surge induces TPH2 expression and de novo 5-HT synthesis; (ii) the induced 5-HT in turn inhibits cortisol secretion by modulating the adrenal sensitivity to ACTH via the suprachiasmatic nuclei (SCN)-SNS-adrenal system, such that it contributes to the feedback inhibition of cortisol production; (iii) basal TPH2 expression or 5-HT synthesis, as well as early-life experience, influence basal cortisol primarily via the hormonal HPA axis; and (iv) 5'- and 3'-regulatory polymorphisms of TPH2 may differentially influence the stress response, presumably due to their differential roles in gene expression regulation. Our increasing knowledge of TPH2 expression regulation not only helps us better understand the 5-HT-stress interaction and the pathophysiology of neuropsychiatric disorders, but also provides new strategies for the treatment of stress-associated diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.