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

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dc.contributor.author Shackleton, Cedric H. L.
dc.contributor.author Neres, Marcos S. [UNIFESP]
dc.contributor.author Hughes, Beuerly A.
dc.contributor.author Stewart, Paul M.
dc.contributor.author Kater, Claudio E. [UNIFESP]
dc.date.accessioned 2016-01-24T13:51:31Z
dc.date.available 2016-01-24T13:51:31Z
dc.date.issued 2008-07-01
dc.identifier http://dx.doi.org/10.1016/j.steroids.2008.02.001
dc.identifier.citation Steroids. New York: Elsevier B.V., v. 73, n. 6, p. 652-656, 2008.
dc.identifier.issn 0039-128X
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/30773
dc.description.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. en
dc.format.extent 652-656
dc.language.iso eng
dc.publisher Elsevier B.V.
dc.relation.ispartof Steroids
dc.rights Acesso restrito
dc.subject 17-hydroxylase deficiency en
dc.subject C17,20-lyase en
dc.subject steroid metabolism en
dc.subject urinary steroids en
dc.title 17-hydroxylase/C17,20-lyase (CYP17) is not the enzyme responsible for side-chain cleavage of cortisol and its metabolites en
dc.type Artigo
dc.rights.license http://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.contributor.institution Univ Birmingham
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.description.affiliation Univ Birmingham, Div Med Sci, Inst Biomed Res, Birmingham B15 2TT, W Midlands, England
dc.description.affiliation Universidade Federal de São Paulo, Div Endocrinol, Dept Med, São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Div Endocrinol, Dept Med, São Paulo, Brazil
dc.identifier.doi 10.1016/j.steroids.2008.02.001
dc.description.source Web of Science
dc.identifier.wos WOS:000255817100010



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