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CYP7B generates a selective estrogen receptor beta agonist in human prostate
Cécile Martin1, Margaret Ross, Karen E Chapman
1Endocrinology Unit, Department of Oncology, University of Edinburgh Western General Hospital, Edinburgh EH4 2XU, United Kingdom. cecile.martin@ed.ac.uk
The Journal of Clinical Endocrinology and Metabolism
|June 8, 2004
Summary
The CYP7B enzyme in the human prostate converts dehydroepiandrosterone (DHEA) into 7alpha-hydroxy-DHEA (7HD), a potent activator of estrogen receptor beta (ERbeta). This enzyme may regulate the balance of androgens and estrogens in the prostate.
Area of Science:
- Endocrinology
- Molecular Biology
- Prostate Cancer Research
Background:
- Dehydroepiandrosterone (DHEA) is a precursor to androgens and estrogens in the prostate.
- CYP7B is a novel P450 enzyme responsible for 7alpha-hydroxylase activity.
- The role of CYP7B in the human prostate was previously uncharacterized.
Purpose of the Study:
- To investigate the expression and function of CYP7B in the human prostate.
- To determine the metabolic fate of DHEA in the human prostate.
- To assess the functional relevance of CYP7B-generated metabolites on sex-steroid receptors.
Main Methods:
- Reverse transcription PCR and mRNA in situ hybridization to detect CYP7B expression.
- Primary cell culture of prostate epithelial cells to measure 7alpha-hydroxylase activity.
- Transient transfections and ligand binding assays to evaluate 7HD's interaction with sex-steroid receptors.
Main Results:
- High levels of CYP7B mRNA were found in epithelial cells of benign prostatic hyperplasia tissue.
- 7alpha-hydroxylation was the predominant metabolic pathway for DHEA in the human prostate.
- 7alpha-hydroxy-DHEA (7HD) specifically activated estrogen receptor beta (ERbeta)-mediated transcription.
Conclusions:
- CYP7B catalyzes the 7alpha-hydroxylation of DHEA in the human prostate epithelium.
- The reaction produces 7HD, an ERbeta-specific agonist.
- CYP7B may represent a novel regulator of the androgen/estrogen balance in the prostate.