Aromatase inhibitors: past, present and future

Area of Science:

• Endocrinology and Molecular Biology
• Biochemistry and Pharmacology

Background:

• The androgen/estrogen ratio is critical for cellular physiology in both sexes.
• Aromatase controls this ratio, making its inhibition vital for treating estrogen-dependent diseases like breast cancer and gynecomastia.
• Estrogens play essential roles in males, including skeletal maturation, bone mineralization, male brain development, and testicular function.

Purpose of the Study:

• To explore various strategies for aromatase inhibition.
• To utilize aromatase inhibitors as tools for studying estrogen's role in adult and developmental physiology.
• To develop and employ novel mammalian models for understanding aromatase active site conformation and designing new inhibitors.

Main Methods:

• Development and characterization of equine aromatase as a mammalian model.
• Site-directed mutagenesis and comparative molecular field analyses.
• Inhibition strategies including antibodies, gene knock-out, antisense oligodeoxynucleotides, and analysis of dietary/environmental compounds.

Main Results:

• Equine aromatase model facilitated testing of hypotheses and design of new inhibitors.
• Demonstrated the essential role of estrogens in male physiology.
• Identified various compounds, including dietary flavonoids and xenobiotics, with antiaromatase effects.

Conclusions:

• Aromatase inhibition is a key therapeutic strategy for estrogen-dependent conditions.
• Aromatase inhibitors are invaluable tools for elucidating estrogen's physiological functions in both sexes.
• Diverse methods, from chemical inhibitors to genetic and antisense approaches, effectively modulate aromatase activity and estrogenic balance.