Document Detail


Sex differences in the regulation of tyrosine hydroxylase gene transcription by estrogen in the locus coeruleus of TH9-LacZ transgenic mice.
MedLine Citation:
PMID:  12225877     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although estrogen is recognized increasingly as having an important role in modulating extrahypothalamic brain function, the mechanisms through which this occur are not well established. The norepinephrine (NE) neurons of the locus coeruleus provide an important neuromodulatory influence upon multiple neural networks throughout the brain and estrogen has been implicated in their regulation. Using a tyrosine hydroxylase (TH) promoter-LacZ transgenic mouse model, which enables rates of TH gene transcription to be examined in vivo, we have examined here whether estrogen regulates expression of the TH gene in the locus coeruleus of males and females. Optical area measurements of Xgal reaction product in the locus coeruleus revealed that gonadectomy exerted opposite effects on TH gene transcription in males and females; transgene expression was increased in males (P<0.01) but reduced in females (P<0.05). Estrogen reversed these effects in both sexes by suppressing gene expression in males (P<0.05) but elevating it in the female (P<0.05). These studies reveal a marked and unexpected sex difference in the regulation of TH gene activity in the mouse. While estrogen in the male, synthesized from circulating testosterone, suppresses TH gene transcription, estrogen in the female enhances TH promoter activity. The present results indicate that estrogen may exert very different sex-dependent effects upon the biosynthesis of NE within the locus coeruleus.
Authors:
Niren R Thanky; Jin H Son; Allan E Herbison
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Brain research. Molecular brain research     Volume:  104     ISSN:  0169-328X     ISO Abbreviation:  Brain Res. Mol. Brain Res.     Publication Date:  2002 Aug 
Date Detail:
Created Date:  2002-09-12     Completed Date:  2002-12-04     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8908640     Medline TA:  Brain Res Mol Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  220-6     Citation Subset:  IM    
Affiliation:
Laboratory of Neuroendocrinology, The Babraham Institute, Cambridge, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Body Weight / drug effects,  physiology
Estrogens / metabolism*,  pharmacology
Estrous Cycle / genetics*
Female
Galactosides / diagnostic use
Gene Expression Regulation / drug effects,  physiology
Genes, Reporter / drug effects,  genetics
Indoles / diagnostic use
Locus Coeruleus / cytology,  drug effects,  enzymology*
Male
Mice
Mice, Transgenic
Neurons / drug effects,  metabolism
Norepinephrine / biosynthesis*
Orchiectomy
Ovariectomy
Promoter Regions, Genetic / drug effects,  genetics
Sex Characteristics*
Transcription, Genetic / drug effects,  genetics*
Transgenes / drug effects,  genetics
Tyrosine 3-Monooxygenase / drug effects,  genetics*
beta-Galactosidase / diagnostic use
Chemical
Reg. No./Substance:
0/Estrogens; 0/Galactosides; 0/Indoles; 51-41-2/Norepinephrine; 7240-90-6/5-bromo-4-chloro-3-indolyl beta-galactoside; EC 1.14.16.2/Tyrosine 3-Monooxygenase; EC 3.2.1.23/beta-Galactosidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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