Steroid 17-hydroxylase and 17,20-lyase deficiencies, genetic and pharmacologic.
J Steroid Biochem Mol Biol
; 165(Pt A): 71-78, 2017 01.
Article
de En
| MEDLINE
| ID: mdl-26862015
ABSTRACT
Steroid 17-hydroxylase 17,20-lyase (cytochrome P450c17, P450 17A1, CYP17A1) catalyzes two major reactions steroid 17-hydroxylation followed by the 17,20-lyase reactions. The most severe mutations in the cognate CYP17A1 gene abrogate all activities and cause combined 17-hydroxylase/17,20-lyase deficiency (17OHD), a biochemical phenotype that is replicated by treatment with the potent CYP17A1 inhibitor abiraterone acetate. The adrenals of patients with 17OHD synthesize 11-deoxycorticosterone (DOC) and corticosterone but no 19-carbon steroids, similar to the rodent adrenal, and DOC causes hypertension and hypokalemia. Loss of 17,20-lyase activity precludes sex steroid synthesis and leads to sexual infantilism. Rare missense CYP17A1 mutations minimally disrupt 17-hydroxylase activity but cause isolated 17,20-lyase deficiency (ILD), Mutations in the POR gene encoding the required cofactor protein cytochrome P450-oxidoreductase causes a spectrum of disease from ILD to 17OHD combined with 21-hydroxylase and aromatase deficiencies, sometimes including skeletal malformations. Mutations in the CYB5A gene encoding a second cofactor protein cytochrome b5 also selectively disrupt 17,20-lyase activity and cause the purest form of ILD. The clinical manifestations of these conditions are best understood in the context of the biochemistry of CYP17A1.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Steroid 17-alpha-hydroxylase
/
Hyperplasie congénitale des surrénales
Limites:
Animals
/
Female
/
Humans
/
Male
Langue:
En
Journal:
J Steroid Biochem Mol Biol
Sujet du journal:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Année:
2017
Type de document:
Article