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

被引：50

作者：

CHANG, YT

ZHANG, L

ALKADDOUR, HS

MASON, JI

LIN, KM

YANG, XJ

GARIBALDI, LR

BOURDONY, CJ

DOLAN, LM

DONALDSON, DL

PANG, SY

机构：

[1] UNIV ILLINOIS, COLL MED, DEPT PEDIAT MC856, DIV PEDIAT ENDOCRINOL, CHICAGO, IL 60612 USA

[2] UNIV TEXAS, SW MED CTR, GREEN CTR REPROD BIOL SCI, DALLAS, TX 75235 USA

[3] CARDINAL GLENNON MEM HOSP CHILDREN, ST LOUIS, MO 63104 USA

[4] SAN JUAN CITY HOSP, DEPT PEDIAT, SAN JUAN, PR USA

[5] CHILDRENS HOSP MED CTR, CINCINNATI, OH 45267 USA

[6] UNIV KANSAS, MED CTR, DEPT PEDIAT, KANSAS CITY, KS 66103 USA

来源：

PEDIATRIC RESEARCH | 1995年 / 37卷 / 06期

关键词：

D O I：

10.1203/00006450-199506000-00024

中图分类号：

R72 [儿科学];

学科分类号：

100202 ;

摘要：

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. This suggests that the moderately decreased adrenal 3 beta-HSD activity in the patient is not due to mild late-onset variants of inherited 3 beta-HSD deficiency CAH, whereas the carriers for true 3 beta-HSD deficiency CAH do not express decreased adrenal 3 beta-HSD activity.

引用

页码：820 / 824

页数：5

共 19 条

[1]

Bongiovanni A.M., The adrenogenital syndrome with deficiency of 3β-hydroxysteroid dehydrogenase, J Clin Invest, 41, pp. 2086-2092, (1962)

[2]

Pang S., Levine L.S., Stoner E., Opitz J.M., Pollack M.S., Dupont B., New M., Nonsalt-losing congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiency with normal glomerulosa function, J Clin Endocrinol Metab, 56, pp. 808-818, (1983)

[3]

De Peretti E., Forest M.G., Feit J.P., David M., Endocrine studies in two children with male pseudohermaphroditism due to 3β-hydroxysteroid (3β-HSD) dehydrogenase defec, Adrenal Androgens, pp. 141-145, (1980)

[4]

Mendonca B., Bloise W., Arnhold I., Batista M., Toledo S., Drummond M., Mattar W., Male pseudohermaphroditism due to nonsalt-wasting 3β-hydroxysteroid dehydrogenase deficiency: Gender role change and absence of gynecomastia at puberty, J Steroid Biochem, 28, pp. 669-675, (1987)

[5]

Rosenfield R.L., Rich B.H., Wolfsdorf J.I., Cassorla F., Parks J.S., Bongiovanni A.M., Wu C.H., Shackleton C.H., Pubertal presentation of congenital A5-3β-hydroxysteroid dehydrogenase deficiency, J Clin Endocrinol Metab, 51, pp. 345-353, (1980)

[6]

Sigel S.F., Finegold D.N., Urban M.D., McVie R., Lee P.A., Premature pubarche: Etiology heterogeneity, J Clin Endocrinol Metab, 74, pp. 239-247, (1992)

[7]

Temeck J.W., Pang S., Nelson C., New M.I., Genetic defects of steroidogenesis in premature pubarche, J Clin Endocrinol Metab, 64, pp. 609-617, (1987)

[8]

Bongiovanni A.M., The response of several adrenocortical steroids to the administration of ACTH in hirsute women, J Steroid Biochem, 18, pp. 745-747, (1983)

[9]

Lobo R.A., Goebelsmann U., Evidence for reduced 3β-ol-hydroxysteroid dehydrogenase activity in some hirsute women thought to have polycystic ovary syndrome, J Clin Endocrinol Metab, 53, pp. 394-400, (1981)

[10]

Pang S., Lerner A.J., Stoner E., Levine L.S., Oberfield S.E., Engel I., New M., Late-onset adrenal steroid 3β-hydroxysteroid dehydrogenase deficiency. I. A cause of hirsutism in pubertal and postpuberal women, J Clin Endocrinol Metab, 60, pp. 428-439, (1985)

← 1 2 →