Indomethacin-sensitive 3 alpha-hydroxysteroid dehydrogenase in rat tissues

Area of Science:

• Biochemistry
• Pharmacology
• Endocrinology

Background:

• 3 alpha-hydroxysteroid dehydrogenase (EC 1.1.1.50) in rat liver cytosol is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs).
• NSAIDs inhibit cyclooxygenase at micromolar concentrations, correlating with their therapeutic potency.

Purpose of the Study:

• To investigate the presence and activity of indomethacin-sensitive 3 alpha-hydroxysteroid dehydrogenase in various rat tissues.
• To determine the effect of indomethacin on androgen and cortisone metabolism in different tissues.

Main Methods:

• Purification of 3 alpha-hydroxysteroid dehydrogenase from rat liver cytosol.
• Assay of enzyme activity and inhibition by indomethacin in seven different rat tissues.
• Measurement of IC50 values for indomethacin inhibition in specific tissues.

Main Results:

• Indomethacin-sensitive 3 alpha-hydroxysteroid dehydrogenase was found in seven rat tissues, including prostate, lung, liver, and testis.
• Prostatic 5 alpha-dihydrotestosterone reduction was inhibited by indomethacin (IC50 = 10 microM).
• Liver, lung, and testis 5 beta-dihydrocortisone reduction showed higher sensitivity to indomethacin (IC50 = 1-3 microM).
• Lung tissue exhibited higher specific activity of indomethacin-sensitive dehydrogenase than prostate and testis.

Conclusions:

• Androgen and cortisone metabolism may be impacted by NSAIDs under conditions of cyclooxygenase inhibition.
• The distribution and activity of indomethacin-sensitive 3 alpha-hydroxysteroid dehydrogenase vary across rat tissues.
• Lung tissue plays a significant role in indomethacin-sensitive dehydrogenase activity, potentially impacting prostaglandin metabolism.