EVIDENCE FOR INDEPENDENT MODULATION OF HUMAN 11-HSD AND 5-ALPHA 5-BETA REDUCTASE ACTIVITIES/

The increased ratio of 5 alpha to 5 beta reduced steroids associated w ith apparent mineralocorticoid excess (AME) may be a necessary consequ ence of altered 11 beta-hydroxysteroid dehydrogenase (11-HSD) activity . In order to test this hypothesis we have compared changes in 11-HSD activity and 5 alpha/5 beta reduction in a variety of clinical and exp erimental conditions. The ratio of 11-oxo/11 beta-hydroxy metabolites of cortisol (11-oxo/11-OH FM) was used as an index of 11-HSD activity and the ratio of allotetrahydrocortisol/ tetrahydrocortisol (allo THF/ THF) was used as an index of 5 alpha/5 beta reduction. Ratios were der ived from 24 hour urinary steroid profiles measured by high resolution gas chromatography. The clinical conditions studied were Gushing's Sy ndrome, Major Depression and hirsutism. In each study, the patient gro up were compared with age-matched healthy controls. For the experiment al conditions, subjects treated with either hydrocortisone, dexamethas one, metyrapone or finasteride acted as their own controls. No consist ent relationship was found between changes in the ratios of 11-oxo/11- OH FM and allo THF/THF. We conclude that there is no evidence of consi stent metabolic interaction between 11-HSD and 5 alpha/5 beta reductas e activities under a wide range of conditions. Furthermore, the patter ns of metabolic changes seen in these conditions are no less character istic, although more subtle, than the well-documented metabolic change s seen in inborn errors of steroid metabolism.