Fertility in patients with genetic deficiencies of cytochrome P450c17 (CYP17A1): combined 17-hydroxylase/17,20-lyase deficiency and isolated 17,20-lyase deficiency.
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.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Kansas, KU Medical Center Office, Kansas City, Kansas.
Courtney A
CA
Marsh
Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan. Electronic address: rauchus@med.umich.edu.
Richard J
RJ
Auchus
D000312:Adrenal Hyperplasia, Congenital / Q000201:enzymology / Q000235:genetics*; D000818:Animals; D005260:Female; D005298:Fertility / Q000235:genetics*; D006801:Humans; D008297:Male; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics* / Q000378:metabolism; D013577:Syndrome
C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase
17-hydroxylase/17,20-lyase; 46,XY DSD; Hypertension; androgen; infertility; mineralocorticoid; primary amenorrhea; sexual infantilism