Inhibition and inactivation of equine aromatase by steroidal and non-steroidal compounds. A comparison with human aromatase inhibition.

This study investigates the impact of certain steroidal and non-steroidal compounds on the functionality of the aromatase enzyme in horses, comparing how similar reactions occur in humans. The research helped to establish detailed understandings of how these compounds connect with and impact aromatase, providing insights into certain structural and functional distinctions between how this enzyme works in different mammals.

Overview of the Research

• The study primarily focused on the impact of three steroidal and three non-steroidal compounds, including 4-hydroxyandrostenedione, 4-acetoxyandrostenedione, 7 alpha-(4′-amino)phenylthio-4-androstene-3, 17-dione, ketoconazole, miconazole, and fadrozole, on the aromatase enzyme in horses.
• The researchers tested these compounds on aromatase found in microorganisms in horse placenta, using this as a standard mammalian model.
• The reactions of these compounds were also tested on microorganisms of human placenta and purified enzyme from horse testicles for comparative purposes.

Findings and Comparisons

• All the test compounds competitively inhibited the aromatase enzyme in horses to varying degrees.
• The non-steroidal derivatives did not inactivate horse aromatase, but the first two steroidal compounds did so to a greater extent than the third one.
• The first steroidal compound equally inhibited the purified, equine and human microsomal aromatases, inhibiting activity by around 90-94%.
• However, the second steroidal compound showed marked differences between the species, inhibiting horse microsomal aromatase at a higher rate (92%) compared to human microsomal aromatase (33%). This compound only inhibited the purified horse enzyme by 40%, which no longer existed in its natural membrane environment.

Significance of the Research

• The comparative study between horse and human microsomal aromatases highlights specific functional and structural differences in how this enzyme works in these different mammals.
• The research potentially contributes to our understanding of the role these compounds can play in influencing enzymic activities, which can have potential applications in the field of veterinary and human medicine.