Inhibition of rat renal and testicular 11 beta-hydroxysteroid dehydrogenase by some antihypertensive drugs, diuretics, and epitestosterone

Horm Metab Res. 1997 Sep;29(9):465-8. doi: 10.1055/s-2007-979079.

Abstract

With regard to previous finding of an inhibitory activity of furosemide on 11 beta-hydroxysteroid dehydrogenase, 16 other commonly used diuretics have been tested as to their ability to inhibit rat renal, and in four instances also testicular 11 beta-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, 11 beta-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 11 beta-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 Ki 850, 1200 nmol/l and Vmax 2420, 3900 nmol/l.min for renal and testicular enzyme, respectively. In contrast to kidneys, the testicular 11 beta-hydroxysteroid dehydrogenase accepted also 11 beta-hydroxy-4-androstene-3,17-dione as a substrate, which could be inhibited by epitestosterone (Ki 1490 nmol/l, Vmax 1150 nmol/l.min). The results represent further evidence for different substrate specificity of renal and testicular 11 beta-hydroxysteroid dehydrogenase.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenases
  • Adrenergic beta-Antagonists / pharmacology
  • Androstenedione / analogs & derivatives
  • Androstenedione / metabolism
  • Animals
  • Antihypertensive Agents / pharmacology*
  • Corticosterone / metabolism
  • Diuretics / pharmacology*
  • Enzyme Inhibitors / pharmacology*
  • Epitestosterone / pharmacology
  • Glycyrrhetinic Acid / pharmacology
  • Hydroxysteroid Dehydrogenases / antagonists & inhibitors*
  • Kidney / enzymology*
  • Kidney / ultrastructure
  • Male
  • Microsomes / enzymology
  • Rats
  • Substrate Specificity
  • Testis / enzymology*

Substances

  • Adrenergic beta-Antagonists
  • Antihypertensive Agents
  • Diuretics
  • Enzyme Inhibitors
  • Androstenedione
  • Epitestosterone
  • 11-hydroxyandrostenedione
  • Hydroxysteroid Dehydrogenases
  • 11-beta-Hydroxysteroid Dehydrogenases
  • Glycyrrhetinic Acid
  • Corticosterone