Regulation of aromatase expression by the nuclear receptor LRH-1 in adipose tissue

Aromatase is the enzyme responsible for estrogen production, and is the product of the CYP19 gene. This gene is under the control of many tissue-specific promoters, each of which is regulated by different cohorts of factors. In normal breast adipose tissue, relatively low levels of aromatase are exp...

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Bibliographic Details
Published in:Molecular and cellular endocrinology 2004-02, Vol.215 (1), p.39-44
Main Authors: Clyne, Colin D., Kovacic, Agnes, Speed, Caroline J., Zhou, Jiong, Pezzi, Vincenzo, Simpson, Evan R.
Format: Article
Language:English
Subjects:
Adipose Tissue
Animals
Aromatase
Aromatase - genetics
Aromatase - metabolism
Breast cancer
Estrogen
Gene Expression Regulation, Enzymologic
Humans
LRH-1
Promoter Regions, Genetic - physiology
Receptors, Cytoplasmic and Nuclear - metabolism
SHP
Transcription Factors - physiology
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Summary:Aromatase is the enzyme responsible for estrogen production, and is the product of the CYP19 gene. This gene is under the control of many tissue-specific promoters, each of which is regulated by different cohorts of factors. In normal breast adipose tissue, relatively low levels of aromatase are expressed via the action of the adipose specific promoter I.4. Breast tumor-derived factors such as prostaglandin E 2 (PGE 2) strongly stimulate aromatase expression via an alternative promoter, promoter II, leading to increased estrogenic drive and tumor growth. Understanding the mechanisms that regulate promoter II activity in tumorous breast may therefore identify new targets for breast cancer drug discovery. The current study describes the role of the orphan nuclear receptor LRH-1 and its co-regulators in modulating aromatase expression in breast adipose tissue.
ISSN:0303-7207
1872-8057
DOI:10.1016/j.mce.2003.11.001