CYP17A1 catalyzes the 17-hydroxylase and 17,20-lyase reactions, regulating the steroid hormones produced by the adrenal glands and gonads. Mutations that compromise all CYP17A1 activities are extremely rare and cause combined 17-hydroxylase/17,20-lyase deficiency. Clinically, combined 17-hydroxylase/17,20-lyase deficiency presents with hypertension, hypokalemia, primary amenorrhea, and sexual infantilism. A few mutations selectively impair 17,20-lyase activity, and some mutations in cofactor proteins cytochrome P450-oxidoreductase and cytochrome b5 also selectively disrupt 17,20-lyase activity. The defect in sex steroid synthesis impairs fertility in both male and female patients when the deficiency is severe. This paper reviews the genetics, steroidogenesis, and fertility impairments associated with these disorders.
Keywords: 17-hydroxylase/17,20-lyase; 46,XY DSD; Hypertension; androgen; infertility; mineralocorticoid; primary amenorrhea; sexual infantilism.
Copyright © 2014. Published by Elsevier Inc.