Journal article
Tissue-specific glucocorticoid regulation of tryptophan hydroxylase mRNA levels
Brain research. Molecular brain research., Vol.48(2), pp.346-354
1997
DOI: 10.1016/S0169-328X(97)00106-X
PMID: 9332732
Abstract
A potential long-term target of glucocorticoid modulation of serotonin (5-HT) production is tryptophan hydroxylase (TPH) gene expression. However, studies on TPH gene expression have been hampered by the extremely low levels of TPH mRNA in the brain, and there have been contradictory reports on the effects of glucocorticoids on 5-HT levels. To overcome these obstacles, we have developed a sensitive competitive RT-PCR assay to directly measure TPH mRNA levels from the rat brain. We observed a tissue-specific modulation of TPH mRNA levels in the melatonin producing pineal gland and the serotonin producing raphe nuclei of the brain. Following chronic treatment of adrenalectomized rats with the synthetic glucocorticoid dexamethasone for 1 week, there was a 16-fold increase in TPH mRNA in the pineal gland that was contrasted by a decrease in TPH mRNA to 16% of the control levels in the brain. To address the mechanism of dexamethasone repression of TPH mRNA levels, we then tested a serotonergic neuronal-like cell line derived from rat thyroid C cells. Dexamethasone caused a rapid decrease in TPH mRNA levels to ≈20% of control values in CA77 C cells. This was measured by both competitive RT-PCR and a standard hybridization assay, which confirmed the validity of the RT-PCR assay. Furthermore, the reduction of TPH mRNA levels was associated with a decrease in 5-HT levels in the CA77 C cells. Hence, glucocorticoids may alter serotonin and melatonin biosynthetic capacity by cell-specific modulation of the TPH gene.
Details
- Title: Subtitle
- Tissue-specific glucocorticoid regulation of tryptophan hydroxylase mRNA levels
- Creators
- Michael S Clark - Molecular Biology Program, University of Iowa, Iowa City, IA 52242, USAAndrew F Russo - Molecular Biology Program, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Brain research. Molecular brain research., Vol.48(2), pp.346-354
- DOI
- 10.1016/S0169-328X(97)00106-X
- PMID
- 9332732
- NLM abbreviation
- Brain Res Mol Brain Res
- ISSN
- 0169-328X
- eISSN
- 1872-6941
- Publisher
- Elsevier B.V
- Language
- English
- Date published
- 1997
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center
- Record Identifier
- 9984020743302771
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