Young J, Couzinet B, Pholsena M, Nahoul K, Labrie F, Schaison G
Service d'Endocrinologie et des Maladies de la Reproduction, Hôpital Bicetre, Kremlin Bicêtre, France.
J Clin Endocrinol Metab. 1994 Feb;78(2):299-304. doi: 10.1210/jcem.78.2.8106615.
There is little information about the plasma concentrations of 3 beta-hydroxy-delta 5-steroids (delta 5-steroids) in untreated patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. To further study the delta 5 pathway, we measured plasma levels of delta 5- and delta 4-steroids in 21 adult patients with different degrees of 21-hydroxylase deficiency (11 salt-wasters, 5 simple virilizers, and 5 patients with the nonclassical form of the disease). In all patients, investigations were performed after withdrawal of steroid treatment for at least 10 days. In addition, catheterization of gonadal and adrenal veins was performed in two salt-wasting male patients displaying bilateral testicular tumors to study adrenal secretion of delta 5- and delta 4-steroids. In one of them, surgical resection of the intratesticular adrenal rests gave the opportunity to measure 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) activity. In all untreated patients, an increase in plasma delta 4-steroids was observed. In contrast, although plasma levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) were not significantly modified in simple virilizers, a paradoxical decrease in all delta 5-steroids was observed in salt-wasters. Catheterization of the adrenal veins confirmed the decrease in delta 5-steroids, particularly DHEA and DHEAS. The androstenedione/DHEA ratio was increased in all patients proportionally to the severity of the disease, suggesting an increase in adrenal 3 beta HSD. In vitro analysis of 3 beta HSD activity showed a 4-fold increase in intratesticular adrenal tissue compared to that in normal adrenals. A positive correlation between the androstenedione/DHEA ratio and plasma ACTH levels was observed, suggesting a long term stimulatory effect of ACTH on 3 beta HSD. Angiotensin-II could have an additive effect on ACTH-induced 3 beta HSD activity.
关于21-羟化酶缺乏所致先天性肾上腺皮质增生症未经治疗患者的血浆3β-羟基-δ5-类固醇（δ5-类固醇）浓度的信息很少。为了进一步研究δ5途径，我们测量了21例不同程度21-羟化酶缺乏的成年患者（11例失盐型、5例单纯男性化型和5例非经典型疾病患者）的血浆δ5-和δ4-类固醇水平。所有患者在停用类固醇治疗至少10天后进行检查。此外，对两名患有双侧睾丸肿瘤的失盐型男性患者进行性腺静脉和肾上腺静脉插管，以研究肾上腺δ5-和δ4-类固醇的分泌。其中一名患者，对睾丸内肾上腺残余组织进行手术切除，得以测量3β-羟类固醇脱氢酶（3βHSD）活性。在所有未经治疗的患者中，均观察到血浆δ4-类固醇增加。相比之下，虽然单纯男性化型患者的脱氢表雄酮（DHEA）和硫酸脱氢表雄酮（DHEAS）血浆水平无显著改变，但在失盐型患者中观察到所有δ5-类固醇均出现反常下降。肾上腺静脉插管证实了δ5-类固醇，特别是DHEA和DHEAS的减少。所有患者的雄烯二酮/DHEA比值均与疾病严重程度成比例增加，提示肾上腺3βHSD增加。3βHSD活性的体外分析显示，睾丸内肾上腺组织的活性比正常肾上腺高4倍。观察到雄烯二酮/DHEA比值与血浆促肾上腺皮质激素（ACTH）水平呈正相关，提示ACTH对3βHSD有长期刺激作用。血管紧张素II可能对ACTH诱导的3βHSD活性有累加作用。
