17-hydroxylase/C17,20-lyase (CYP17) is not the enzyme responsible for side-chain cleavage of cortisol and its metabolites

17-hydroxylase/C17,20-lyase (CYP17) is not the enzyme responsible for side-chain cleavage of cortisol and its metabolites

Author Shackleton, Cedric H. L. Google Scholar
Neres, Marcos S. Autor UNIFESP Google Scholar
Hughes, Beuerly A. Google Scholar
Stewart, Paul M. Google Scholar
Kater, Claudio E. Autor UNIFESP Google Scholar
Institution Univ Birmingham
Universidade Federal de São Paulo (UNIFESP)
Abstract The question addressed in this study was the nature of the enzyme required to remove the side-chain of 17-hydroxycorticosteroids, leading in the case of cortisol to the excretion of 11 beta-hydroxyandrosterone, 11-oxo-androsterone and the corresponding etiocholanolones. We questioned whether it could be CYP17, the 17-hydroxylase/17,20-lyase utilized in androgen synthesis. the conversion of exogenous cortisol to C-19 steroids in patients with complete 17-hydroxylase deficiency (17HD) was studied rationalizing that if CYP17 was involved no C-19 steroids would be formed. the urinary excretion of the four 11-oxy-C-19 steroids as well as many of the major C-21 cortisol metabolites were measured by GC/MS. Our results showed that the conversion of cortisol to C-19 steroids was normal in 17HD indicating that a currently unidentified enzyme must be responsible for this transformation.A secondary goal was to determine to what extent 11-oxy-C-19 steroids were metabolites of cortisol or adrenal synthesized 11 beta-hydroxyandrostenedione. Since cortisol-treated 17HD patients cannot produce androstenedione, all C-19 11-oxy-metabolites excreted must be derived from exogenous cortisol. the extent to which 17HD patients have lower relative excretion of C-19 steroids should reflect the absence of lip-hydroxyandrostenedione metabolites. Our results showed almost all of 11-oxo-etiocholanolone and 11 beta-hydroxyetiocholanolone were cortisol metabolites, but in contrast the excretion of lip-hydroxyandrosterone was less than 10% that of normal individuals, indicating that in excess of 90% must be a metabolite of 11 beta-hydroxyandrostenedione. (C) 2008 Elsevier Inc. All rights reserved.
Keywords 17-hydroxylase deficiency
C17,20-lyase
steroid metabolism
urinary steroids
Language English
Date 2008-07-01
Published in Steroids. New York: Elsevier B.V., v. 73, n. 6, p. 652-656, 2008.
ISSN 0039-128X (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 652-656
Origin http://dx.doi.org/10.1016/j.steroids.2008.02.001
Access rights Closed access
Type Article
Web of Science ID WOS:000255817100010
URI http://repositorio.unifesp.br/handle/11600/30773

Show full item record




File

File Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)

Search


Browse

Statistics

My Account