Please use this identifier to cite or link to this item: http://repositorio.unifesp.br/handle/11600/30773
Title: 17-hydroxylase/C17,20-lyase (CYP17) is not the enzyme responsible for side-chain cleavage of cortisol and its metabolites
Authors: Shackleton, Cedric H. L.
Neres, Marcos S. [UNIFESP]
Hughes, Beuerly A.
Stewart, Paul M.
Kater, Claudio E. [UNIFESP]
Univ Birmingham
Universidade Federal de São Paulo (UNIFESP)
Keywords: 17-hydroxylase deficiency
C17,20-lyase
steroid metabolism
urinary steroids
Issue Date: 1-Jul-2008
Publisher: Elsevier B.V.
Citation: Steroids. New York: Elsevier B.V., v. 73, n. 6, p. 652-656, 2008.
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.
URI: http://repositorio.unifesp.br/handle/11600/30773
ISSN: 0039-128X
Other Identifiers: http://dx.doi.org/10.1016/j.steroids.2008.02.001
Appears in Collections:Em verificação - Geral

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