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PMID: 2884660 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Transcriptional regulation of the tyrosine hydroxylase gene by glucocorticoid and cyclic AMP.

Lewis EJ, Harrington CA, Chikaraishi DM

Abstract

Glucocorticoid and cyclic AMP increase tyrosine hydroxylase (TH) activity and mRNA levels in pheochromocytoma cultures. The transcriptional activity of the TH gene, as measured by nuclear run-on assay, is also increased when cultures are treated with the synthetic glucocorticoid dexamethasone or agents that increase intracellular cyclic AMP, such as forskolin and 8-BrcAMP. Both inducers effect transcriptional changes within 10 min after treatment and are maximal after 30 min for forskolin and after 60 min for dexamethasone. The 5' flanking sequences of the TH gene were fused to the bacterial gene chloramphenicol acetyltransferase (CAT), and the hybrid gene was transfected into pheochromocytoma cultures and GH4 pituitary cells. In both cell lines, a region of the TH gene containing bases -272 to +27 conferred induction of CAT by cyclic AMP, but not by glucocorticoid. The same results were found when a region of the TH gene containing -773 to +27 was used. Thus, the sequences required for induction of TH by cyclic AMP are contained within 272 bases of 5' flanking sequence, but sequences sufficient for glucocorticoid regulation are not contained within 773 bases.

MeSH Terms
8-Bromo Cyclic Adenosine Monophosphate/pharmacology Adrenal Gland Neoplasms Animals Base Sequence Cell Line Cloning, Molecular Colforsin/pharmacology Cyclic AMP/metabolism Dexamethasone/pharmacology Gene Expression Regulation/drug effects Genes/drug effects Genes, Regulator Kinetics Pheochromocytoma Transcription, Genetic/drug effects Tyrosine 3-Monooxygenase/genetics
Chemicals
Colforsin 8-Bromo Cyclic Adenosine Monophosphate Dexamethasone Cyclic AMP Tyrosine 3-Monooxygenase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lewis E J
Harrington C A
Chikaraishi D M
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47 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1987-06-00
Pages
3550-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC304912
Subset
IM
Grants
NINDS NIH HHS · NS22675 · United States
Databases
GENBANK
M16473
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