title: Absence of molecular defect in the type II 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) gene in premature pubarche children and hirsute female patients with moderately decreased adrenal 3 beta-HSD activity.
abstract: To date the molecular basis and hormonal criteria for inherited mild late-onset 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency congenital adrenal hyperplasia (CAH) have not been defined. We have thus investigated the presence or absence of mutation in the type II 3 beta-HSD gene encoding adrenal/gonadal 3 beta-HSD in each of five premature pubarche children and hirsute female patients manifesting moderately decreased adrenal 3 beta-HSD activity. ACTH-stimulated hormonal levels in all patients compared with mean levels in pubertal stage-matched normal subjects were between 2.5 and 6.5 SD for 17-hydroxypregnenolone levels, and between 2.5 and 7 SD for dehydroepiandrosterone levels in all except one patient. 17-Hydroxypregnenolone to cortisol ratios were between 2.5 and 4.3 SD, and dehydroepiandrosterone to androstenedione ratios were between 3 and 8.6 SD. The type II 3 beta-HSD gene regions of a putative promoter, exons I, II, III, and IV, and exon-intron boundaries in all subjects were amplified by polymerase chain reaction and then sequenced. All patients had normal sequences of the type II 3 beta-HSD gene in both alleles. Three female patients heterozygotic for severe 3 beta-HSD deficiency CAH with one allele mutation of the gene demonstrated normal ACTH-stimulated hormone profiles. These data indicate that moderately decreased adrenal 3 beta-HSD activity resulting in modestly increased delta 5 precursor steroid levels and delta 5 to delta 4 steroid ratios in premature pubarche and hirsute patients is not caused by a mutation in the type II 3 beta-HSD gene.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Pediatric Endocrinology, University of Illinois, College of Medicine at Chicago 60612, USA.
authors.forename: Y T
authors.initials: YT
authors.lastname: Chang
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: H S
authors.initials: HS
authors.lastname: Alkaddour
authors.forename: J I
authors.initials: JI
authors.lastname: Mason
authors.forename: K
authors.initials: K
authors.lastname: Lin
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.forename: L R
authors.initials: LR
authors.lastname: Garibaldi
authors.forename: C J
authors.initials: CJ
authors.lastname: Bourdony
authors.forename: L M
authors.initials: LM
authors.lastname: Dolan
authors.forename: D L
authors.initials: DL
authors.lastname: Donaldson
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000172:deficiency / Q000235:genetics*; D000293:Adolescent; D000324:Adrenocorticotropic Hormone; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005091:Exons; D005260:Female; D005815:Genetic Code; D006628:Hirsutism / Q000235:genetics*; D006801:Humans; D007438:Introns; D017354:Point Mutation; D011629:Puberty, Precocious / Q000235:genetics*; D013268:Stimulation, Chemical
chemical_list: D000324:Adrenocorticotropic Hormone; D015096:3-Hydroxysteroid Dehydrogenases