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: Y T Chang, L Zhang, H S Alkaddour, J I Mason, K Lin, X Yang, L R Garibaldi, C J Bourdony, L M Dolan, D L Donaldson
• Journal: Pediatric research (Pediatr Res) Vol. 37 Issue 6 Pg. 820-4 (Jun 1995) ISSN: 0031-3998 [Print] United States
• PMID: 7651769 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adrenocorticotropic Hormone
• 3-Hydroxysteroid Dehydrogenases

Topics

• 3-Hydroxysteroid Dehydrogenases (deficiency, genetics)
• Adolescent
• Adrenocorticotropic Hormone
• Adult
• Base Sequence
• Child
• Child, Preschool
• Exons
• Female
• Genetic Code
• Hirsutism (genetics)
• Humans
• Introns
• Point Mutation
• Puberty, Precocious (genetics)
• Stimulation, Chemical