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Evidence for independent modulation of human 11-HSD and 5 alpha/5 beta reductase activities.

Authors
  • Raven, P W
  • Taylor, N F
Type
Published Article
Journal
Endocrine research
Publication Date
Nov 01, 1996
Volume
22
Issue
4
Pages
811–815
Identifiers
PMID: 8969944
Source
Medline
License
Unknown

Abstract

The increased ratio of 5 alpha to 5 beta reduced steroids associated with apparent mineralocorticoid excess (AME) may be a necessary consequence 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 experimental 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 derived from 24 hour urinary steroid profiles measured by high resolution gas chromatography. The clinical conditions studied were Cushing's Syndrome, Major Depression and hirsutism. In each study, the patient group were compared with age-matched healthy controls. For the experimental conditions, subjects treated with either hydrocortisone, dexamethasone, metyrapone or finasteride acted as their own controls. No consistent 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 consistent metabolic interaction between 11-HSD and 5 alpha/5 beta reductase activities under a wide range of conditions. Furthermore, the patterns of metabolic changes seen in these conditions are no less characteristic, although more subtle, than the well-documented metabolic changes seen in inborn errors of steroid metabolism.

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