title: The biochemical and phenotypic characterization of females homozygous for 5 alpha-reductase-2 deficiency.
abstract: The biochemical and physiologic manifestations of decreased 5 alpha-dihydrotestosterone (DHT) in females are characterized. Three females from the large Dominican kindred with 5 alpha-reductase-2 deficiency were identified as homozygous for a point mutation (R246W, C-->T) on exon 5 of the 5 alpha-reductase-2 gene by single strand DNA conformational polymorphism analysis and DNA sequence analysis. Body hair was decreased; there was no history of acne. Despite delayed menarche, all were fertile, and two had twins. Urinary 5 beta/5 alpha C19 and C21 steroid metabolite ratios were elevated. Plasma testosterone was normal to elevated, with low DHT, resulting in an increased testosterone/DHT ratio. 3 alpha,5 alpha-Androstanediol glucuronide was low. Menstrual cycle profiling performed in two subjects showed ovulatory gonadotropin peaks. Sebum production was normal. 5 alpha-Reductase-2-deficient homozygotic females demonstrate the importance of DHT in the physiology and pathophysiology of body hair growth. Normal sebum implies regulation by the 5 alpha-reductase-1 isoenzyme. Delayed puberty suggests involvement of 5 alpha-reductase-2 in menarche at the hypothalamic/pituitary and/or ovarian level. As two had nonidentical twins, DHT and/or the DHT/estradiol ratio may regulate follicular development, with lower levels permitting more than one dominant follicle per cycle and higher levels impairing follicular development and ovulation. Thus, females with 5 alpha-reductase-2 deficiency highlight a role for DHT in hirsutism and/or menstrual disorders.
authors.affiliation: Department of Medicine, Cornell University Medical College, New York, New York 10021, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Katz
authors.forename: L Q
authors.initials: LQ
authors.lastname: Cai
authors.forename: Y S
authors.initials: YS
authors.lastname: Zhu
authors.forename: C
authors.initials: C
authors.lastname: Herrera
authors.forename: M
authors.initials: M
authors.lastname: DeFillo-Ricart
authors.forename: C H
authors.initials: CH
authors.lastname: Shackleton
authors.forename: J
authors.initials: J
authors.lastname: Imperato-McGinley
mesh_terms: D000328:Adult; D001483:Base Sequence; D001769:Blood / Q000378:metabolism; D042944:Cholestenone 5 alpha-Reductase; D004247:DNA / Q000235:genetics; D012734:Disorders of Sex Development / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008597:Menstrual Cycle / Q000097:blood; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000172:deficiency* / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D012629:Sebum / Q000378:metabolism; D014556:Urine / Q000737:chemistry
chemical_list: D015335:Molecular Probes; D004247:DNA; D010088:Oxidoreductases; D042944:Cholestenone 5 alpha-Reductase