Distinctive profile of the 17-hydroxylase and 17,20-lyase activities revealed by urinary steroid metabolomes of patients with CYP17 deficiency

Distinctive profile of the 17-hydroxylase and 17,20-lyase activities revealed by urinary steroid metabolomes of patients with CYP17 deficiency

Alternative title Perfil característico das atividades 17-hidroxilase e 17,20-liase reveladas por meio do metaboloma de esteroides urinários de pacientes com deficiência de CYP17
Author Neres, Marcos S. Autor UNIFESP Google Scholar
Auchus, Richard J. Google Scholar
Shackleton, Cedric H. L. Google Scholar
Kater, Claudio Elias Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
University of Texas Southwestern Medical Center Department of Clinical Sciences
University of Birmingham Division of Medical Sciences
Abstract OBJECTIVES: (1) Characterize serum (S) and urinary (U) steroid metabolites in complete CYP17 deficiency (cCYP17D); (2) analyze the relative 17α-hydroxylase (17OH) and 17,20-lyase (17,20L) activities in vivo; and (3) comparedata from the two most prevalent mutations in Brazil. SUBJECTS AND METHODS: 20 genotyped cCYP17D patients from a previously reported cohort were homozygous for W406R or R362C; 11 controls were CYP17 wild types (WT). WT and cCYP17D patients had S and U samples drawn to measure: cortisol (F), corticosterone (B), deoxycorticosterone (DOC), 18OH-B, 18OH-DOC, and 17OHP; and tetrahydro (TH)-B, THA, THDOC, THF+5α-THF, TH-cortisone, androsterone, etiocholanolone, 5-pregnenediol, 17OH-pregnenolone and pregnanetriol. RESULTS: Compared to WT, cCYP17D patients had marked elevations of B, DOC, 18OH-B and 18OH-DOC, whereas 17OHP, F and adrenal androgens (AA) were reduced; U steroids parallel S findings. Metabolite ratios revealed that both 17OH and 17,20L activities were impaired in cCYP17D. There were nodifferences between W406R andR362C mutations. CONCLUSIONS: cCYP17D patients show parallel overproduction/overexcretion of 17-deoxysteroids, and marked reduction of F and AA. In addition to 17OH, 17,20-L activity was also impaired in cCYP17D. W406 and R362C mutations disclose similar Sand U patterns.

OBJETIVOS: (1) Caracterizar os esteroides séricos (S) e urinários (U) na deficiência completa da CYP17 (DcCYP17); (2) analisar as atividades da 17α-hidroxilase (17OH) e 17,20-liase (17, 20 L) in vivo; e (3) comparar as duas mutações mais prevalentes no Brasil. SUJEITOS E MÉTODOS: 20 pacientes genotipados para a DcCYP17, de uma coorte anterior, eram homozigotos para W406R ou R362C (8 cada); 11 controles eram CYP17 wild types (WT). Amostras de S e U foram colhidas dos WT e pacientes para dosagem de: cortisol (F), corticosterona (B), deoxicorticosterona (DOC), 18-OH-B, 18OH-DOC e 17OHP; e tetraidro(TH)-B, THA, TH-DOC, THF+5α-THF, THE, androsterona, etiocolanolona, 5-pregnenediol, 17OH-pregnenolona e pregnanetriol. RESULTADOS: Comparados aos WT, os pacientes com DcCYP17 revelaram elevações acentuadas de B, DOC, 18OHB e 18OHDOC, enquanto 17OHP, F e andrógenos adrenais (AA) estavam reduzidos. Os esteroides na U acompanham os achados no S. As relações de metabólitos mostraram que as atividades de 17OH e 17,20L estavam reduzidas em pacientes com DcCYP17. Não houve diferenças entre pacientes com as mutações W406R e R362C. CONCLUSÕES: Na DcCYP17, a produção e a excreção dos 17-deoxiesteroides estão aumentadas em paralelo, em contraste com a reduzida produção/excreção de F e AA. As atividades da 17OH e 17,20-L estão diminuídas na DcCYP17. As mutações W406 e R362C apresentam achados semelhantes em S e U.
Keywords Congenital adrenal hyperplasia
17-hydroxylase deficiency
17,20-lyase deficiency
urinary steroid metabolome
Hiperplasia adrenal congênita
deficiência de 17-hidroxilase
deficiência de 17,20-liase
metaboloma de esteroides urinários
Language English
Date 2010-12-01
Published in Arquivos Brasileiros de Endocrinologia & Metabologia. Sociedade Brasileira de Endocrinologia e Metabologia, v. 54, n. 9, p. 826-832, 2010.
ISSN 0004-2730 (Sherpa/Romeo, impact factor)
Publisher Sociedade Brasileira de Endocrinologia e Metabologia
Extent 826-832
Origin http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-27302010000900009
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000286868900009
SciELO ID S0004-27302010000900009 (statistics in SciELO)
URI http://repositorio.unifesp.br/handle/11600/6087

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