Zerah M, Rhéaume E, Mani P, Schram P, Simard J, Labrie F, New M I
Department of Pediatrics, New York Hospital-Cornell Medical Center, New York 10021.
J Clin Endocrinol Metab. 1994 Dec;79(6):1811-7. doi: 10.1210/jcem.79.6.7989489.
Nonclassical 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase deficiency (NC3 beta HSDD) has been diagnosed in hyperandrogenic women with an increasing frequency during the last 14 yr. Fifteen menarcheal women with androgen excess syndrome, diagnosed with NC3 beta HSDD previously were restudied, in 12 after discontinuation of glucocorticoid treatment, in 2 patients never treated with glucocorticoids, and in 1 both before and after glucocorticoid therapy. Each of the 15 patients underwent ACTH stimulation testing, in some cases on multiple occasions. Although some (very few) patients seem to have improved with time, others remained the same or got worse. Molecular DNA analysis was also performed in 6 of the patients, using the strategy successfully used to detect point mutations in the type II 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) gene, which are responsible for classical 3 beta HSD deficiency. This strategy consists of the direct sequencing of polymerase chain reaction-amplified DNA fragments corresponding to the complete coding sequence and all intron-exon junctions and to the 5'- and 3'-noncoding region of this gene. We were unable to demonstrate any mutation of the type II 3 beta HSD gene in these 6 patients. To gain additional information about potential mutations, direct sequencing of the type I 3 beta HSD gene was also performed using this same strategy, and no mutations were found. The present study strongly suggests that unlike the salt-losing and nonsalt-losing forms of classical 3 beta HSD deficiency, NC3 beta HSDD is not due to a mutant type II 3 beta HSD enzyme. However, the possibility remains of a mutation(s) in the unsequenced regions of the type II 3 beta HSD gene or elsewhere, such as in a gene for modulatory protein, playing a specific role in the expression of the type II 3 beta HSD gene. On the other hand, knowing the multiple hormonal controls to which 3 beta HSD activity is subject, it cannot be excluded that at least in some cases, NC3 beta HSDD may be an acquired defect, the result of endogenous or environmental factors.
在过去14年中，非经典型3β-羟类固醇脱氢酶/δ5-δ4-异构酶缺乏症（NC3βHSDD）在高雄激素血症女性中的诊断频率不断增加。对15名先前被诊断为NC3βHSDD的初潮期雄激素过多综合征女性进行了重新研究，其中12名在停用糖皮质激素治疗后进行研究，2名从未接受过糖皮质激素治疗的患者进行研究，1名患者在糖皮质激素治疗前后均进行了研究。15名患者均接受了促肾上腺皮质激素（ACTH）刺激试验，在某些情况下进行了多次。尽管一些（非常少）患者似乎随时间有所改善，但其他患者情况保持不变或恶化。还对6名患者进行了分子DNA分析，采用了成功用于检测II型3β-羟类固醇脱氢酶（3βHSD）基因点突变的策略，该基因负责经典型3βHSD缺乏症。该策略包括对与完整编码序列、所有内含子-外显子连接以及该基因的5'-和3'-非编码区域相对应的聚合酶链反应扩增DNA片段进行直接测序。我们未能在这6名患者中证明II型3βHSD基因存在任何突变。为了获得有关潜在突变的更多信息，还使用相同策略对I型3βHSD基因进行了直接测序，未发现突变。本研究强烈表明，与经典型3βHSD缺乏症的失盐型和非失盐型不同，NC3βHSDD并非由突变的II型3βHSD酶引起。然而，II型3βHSD基因未测序区域或其他地方（如调节蛋白基因）存在突变并在II型3βHSD基因表达中发挥特定作用的可能性仍然存在。另一方面，鉴于3βHSD活性受到多种激素控制，不能排除至少在某些情况下，NC3βHSDD可能是一种后天缺陷，是内源性或环境因素的结果。
