DOI: 10.1046/j.1471-4159.2003.01944.x. Glucocorticoid‐regulated human serotonin transporter (5‐HTT) expression is modulated by the 5‐HTT gene‐promotor‐linked polymorphic region

Glucocorticoid‐regulated human serotonin transporter (5‐HTT) expression is modulated by the 5‐HTT gene‐promotor‐linked polymorphic region

10.1046/j.1471-4159.2003.01944.x

Crossref journal-article

Wiley

Journal of Neurochemistry (311)

Abstract

AbstractMood, emotion and cognition are modulated by serotonergic neurotransmission, while the physiological function of serotonergic synapses depends on serotonin reuptake, which is mediated by the serotonin transporter (5‐HTT). Allelic variation of 5‐HTT expression in humans is caused by a functional gene‐promoter polymorphism with two predominant variant alleles, which are associated with variations in anxiety measures as previously reported. Here we report that administration of dexamethasone, a potent glucocorticosteroid hormone, results in an increase in 5‐HTT expression in immortalized human B‐lymphoblastoid cells, which express the human 5‐HTT. Functional reporter gene assays as well as 5‐HT uptake and inhibitor binding measures revealed a genotype‐dependent dose–response to glucocorticosteroid administration, which was antagonized by RU 38486, a non‐specific glucocorticosteroid hormone antagonist. The allele‐specific differences after administration of dexamethasone depended on the repetitive GC‐rich sequence located approximately 1.4 kb upstream of the 5‐HTT gene transcription site because of absence of a significant steroid effect after transfecting a deletional mutant reporter gene construct, which lacks this repetitive promoter sequence. Our findings may contribute to explain the vulnerability to stress‐related disorders in susceptible individuals, in whom further clinical studies should follow up on these in vitro findings.

Bibliography

Glatz, K., MÃ¶ssner, R., Heils, A., & Lesch, K. P. (2003). Glucocorticoidâregulated human serotonin transporter (5âHTT) expression is modulated by the 5âHTT geneâpromotorâlinked polymorphic region. Journal of Neurochemistry, 86(5), 1072â1078. Portico.

Authors 4

K. Glatz (first)
R. Mössner (additional)
A. Heils (additional)
K. P. Lesch (additional)

References 38 Referenced 96

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Dates

Type	When
Created	15 years, 1 month ago (July 16, 2010, 1:12 a.m.)
Deposited	1 year, 10 months ago (Oct. 15, 2023, 7:56 a.m.)
Indexed	1 day, 16 hours ago (Sept. 4, 2025, 9:12 a.m.)
Issued	22 years ago (Aug. 11, 2003)
Published	22 years ago (Aug. 11, 2003)
Published Online	22 years ago (Aug. 11, 2003)
Published Print	22 years ago (Sept. 1, 2003)

Funders 0

None

BibTeX

@article{Glatz_2003, title={Glucocorticoid‐regulated human serotonin transporter (5‐HTT) expression is modulated by the 5‐HTT gene‐promotor‐linked polymorphic region}, volume={86}, ISSN={1471-4159}, url={http://dx.doi.org/10.1046/j.1471-4159.2003.01944.x}, DOI={10.1046/j.1471-4159.2003.01944.x}, number={5}, journal={Journal of Neurochemistry}, publisher={Wiley}, author={Glatz, K. and Mössner, R. and Heils, A. and Lesch, K. P.}, year={2003}, month=aug, pages={1072–1078} }

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