abiraterone-acetate and Infertility

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 b

Topics: Abiraterone Acetate; Adrenal Hyperplasia, Congenital; Animals; Antihypertensive Agents; Corticosterone; Cytochromes b5; Desoxycorticosterone; Female; Genotype; Glucocorticoids; Gonadotropins; Humans; Hypertension; Hypospadias; Infertility; Male; Mineralocorticoids; Mutation; Mutation, Missense; Oxidation-Reduction; Steroid 17-alpha-Hydroxylase; Steroid 21-Hydroxylase