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Aromatase inhibitors and enzyme stability.
N Harada1, S I Honda, O Hatano
1Department of Biochemistry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Endocrine-Related Cancer
|March 24, 2000
Summary
Aromatase inhibitors increase aromatase protein by reducing its degradation, not by increasing its production. This effect was observed in vitro and in vivo, suggesting stabilization of aromatase protein.
Area of Science:
- Endocrinology
- Molecular Biology
- Pharmacology
Background:
- Aromatase is a key enzyme in estrogen biosynthesis.
- Aromatase inhibitors are used in treating hormone-dependent cancers.
- The regulation of aromatase expression by inhibitors is not fully understood.
Purpose of the Study:
- To investigate the effects of steroidal and non-steroidal aromatase inhibitors on aromatase mRNA and protein levels.
- To elucidate the mechanism by which aromatase inhibitors affect aromatase expression in vitro and in vivo.
Main Methods:
- In vitro studies using JEG-3 cells treated with various aromatase inhibitors.
- Quantification of aromatase protein via ELISA and mRNA levels.
- In vivo studies involving daily injection of inhibitors into adult female mice.
Main Results:
- Non-steroidal aromatase inhibitors increased aromatase protein levels in JEG-3 cells without altering mRNA levels.
- The increase in aromatase protein was not blocked by cycloheximide, indicating reduced degradation.
- In vivo, inhibitors increased both aromatase mRNA and protein in mouse ovaries.
Conclusions:
- Aromatase inhibitors increase aromatase protein levels primarily through stabilization and reduced protein turnover.
- The observed in vivo increase in mRNA may be secondary to hormonal feedback mechanisms.
- Findings suggest a novel regulatory mechanism for aromatase expression.