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.
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)
Chang
Y T
YT
Division of Pediatric Endocrinology, University of Illinois, College of Medicine at Chicago 60612, USA.
Zhang
L
L
Alkaddour
H S
HS
Mason
J I
JI
Lin
K
K
Yang
X
X
Garibaldi
L R
LR
Bourdony
C J
CJ
Dolan
L M
LM
Donaldson
D L
DL
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
D000324:Adrenocorticotropic Hormone; D015096:3-Hydroxysteroid Dehydrogenases