Inhibition of Rat Renal and Testicular 11β-Hydroxysteroid Dehydrogenase by Some Antihypertensive Drugs, Diuretics, and Epitestosterone

With regard to previous finding of an inhibitory activity of furosemide on 11β-hydroxysteroid dehydrogenase, 16 other commonly used diuretics have been tested as to their ability to inhibit rat renal, and in four instances also testicular 11β-hydroxysteroid dehydrogenase, using glycerrhetinic acid as a standard. In addition, epitestosterone has been tested as well, with respect to its recently demonstrated inhibitory activity on several other enzymes of androgen biosynthesis. Besides corticosterone, 11β-hydroxy-4-androstene-3,17-dione has been used as a substrate. Of all drugs studied, quinapril, dihydralazin, trandolapril, metipamid, methyldopa, betaxolol only appeared to be weak inhibitors of 11β-hydroxysteroid dehydrogenase, with an inhibitory activity 10-28% of that of glycyrrhetinic acid. Using corticosterone as a substrate, epitestosterone displayed a weak inhibitory activity with K_i 850, 1200 nmol/l and V_max 2420, 3900 nmol/l · min for renal and testicular enzyme, respectively. In contrast to kidneys, the testicular 11β-hydroxysteroid dehydrogenase accepted also 11β-hydroxy-4-androstene-3,17-dione as a substrate, which could be inhibited by epitestosterone (K_i 1490 nmol/l, V_max 1150 nmol/l · min). The results represent further evidence for different substrate specificity of renal and testicular 11β-hydroxysteroid dehydrogenase.

Corticosterone - 11β-Hydroxyandrostenedione - Enzyme - Mineralocorticoid - Glucocorticoid