The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
Testosterone Induces Molecular Changes in Dopamine Signaling Pathway Molecules in the Adolescent Male Rat Nigrostriatal Pathway
Open accessAbstract
Adolescent males have an increased risk of developing schizophrenia, implicating testosterone in the precipitation of dopamine-related psychopathology. Evidence from adult rodent brain indicates that testosterone can modulate nigrostriatal dopamine. However, studies are required to understand the role testosterone plays in maturation of dopamine pathways during adolescence and to elucidate the molecular mechanism(s) by which testosterone exerts its effects. We hypothesized that molecular indices of dopamine neurotransmission [synthesis (tyrosine hydroxylase), breakdown (catechol-O-methyl transferase; monoamine oxygenase), transport [vesicular monoamine transporter (VMAT), dopamine transporter (DAT)] and receptors (DRD1-D5)] would be changed by testosterone or its metabolites, dihydrotestosterone and 17β-estradiol, in the nigrostriatal pathway of adolescent male rats. We found that testosterone and dihydrotestosterone increased DAT and VMAT mRNAs in the substantia nigra and that testosterone increased DAT protein at the region of the cell bodies, but not in target regions in the striatum. Dopamine receptor D2 mRNA was increased and D3 mRNA was decreased in substantia nigra and/or striatum by androgens. These data suggest that increased testosterone at adolescence may change dopamine responsivity of the nigrostriatal pathway by modulating, at a molecular level, the capacity of neurons to transport and respond to dopamine. Further, dopamine turnover was increased in the dorsal striatum following gonadectomy and this was prevented by testosterone replacement. Gene expression changes in the dopaminergic cell body region may serve to modulate both dendritic dopamine feedback inhibition and reuptake in the dopaminergic somatodendritic field as well as dopamine release and re-uptake dynamics at the presynaptic terminals in the striatum. These testosterone-induced changes of molecular indices of dopamine neurotransmission in males are primarily androgen receptor-driven events as estradiol had minimal effect. We conclude that nigrostriatal responsivity to dopamine may be modulated by testosterone acting via androgen receptors to alter gene expression of molecules involved in dopamine signaling during adolescence.
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“For example, castration or testosterone injections during mid to late adolescence (p45-p60) alter various markers of dopaminergic function in male rats (Purves-Tyson et al., 2014), though gonadal hormones are not necessary for male-specific peaks in striatal dopamine receptor expression (Andersen et al., 2002).”
From Does puberty mark a transition in sensitive periods for plasticity in the associative neocortex? (2017) · cites this paper as Purves-Tyson et al., 2014
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Kanwore, K., Kanwore, K., Guo, X., Xia, Y., Zhou, H., Zhang, L., Adzika, G. K., Joseph, A.-A., Abiola, A. A., Peipei, M., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24309956
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Role of 5α-reductase inhibitors in Parkinson's disease: Gambling or not?
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Testosterone replacement therapy in Parkinson’s disease a narrative review of current evidence
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Gill, K. E. (2015) · UKnowledge (University of Kentucky)
Metadata
- Authors
- Purves-Tyson, T. D., Owens, S. J., Double, K. L., Desai, R., Handelsman, D. J., & Weickert, C. S.
- Affiliations
- UNSW Sydney (AU)
- The University of Sydney (AU)
- Corresponding author
- Purves-Tyson, Tertia D.
- Owens, Samantha J.
- Double, Kay L.
- Desai, Reena
- Handelsman, David J.
- Weickert, Cynthia Shannon
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-03-11
- Volume
- 9
- Issue
- 3
- Pages
- e91151
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3949980
- OpenAlex
- W2003231418
- Cited by
- 109
- References
- 66
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 7 · 2023: 11 · 2022: 6 · 2021: 7 · 2020: 11 · 2019: 13 · 2018: 9 · 2017: 12 · 2016: 7 · 2015: 5 · 2014: 4
- FWCI
- 4.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UNSWorks (UNSW Sydney) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Neuroscience Research Australia
- University of New South Wales
- NSW Ministry of Health
- Macquarie Group Foundation
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- testosterone, dopamine signaling, nigrostriatal pathway, adolescence, dopamine transporter, vesicular monoamine transporter, dopamine receptors, dopamine D2 receptor, dopamine D3 receptor, dihydrotestosterone, estradiol, androgen receptor, substantia nigra, dorsal striatum, dopamine turnover, schizophrenia risk, gonadectomy, gene expression
- MeSH terms
- Animals, Corpus Striatum, Dopamine, Gene Expression Regulation, Male, Synaptic Transmission, Orchiectomy, Receptors, Dopamine, RNA, Messenger, Gonadal Steroid Hormones, Substantia Nigra, Testosterone, Signal Transduction, Dopamine Plasma Membrane Transport Proteins, Rats
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