Sakai Y, Yanase T, Okabe Y, Hara T, Waterman M R, Takayanagi R, Haji M, Nawata H
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
J Clin Endocrinol Metab. 1994 Oct;79(4):1198-201. doi: 10.1210/jcem.79.4.7962293.
Molecular basis of lipoid adrenal hyperplasia (lipoid CAH) in a Japanese patient was investigated. A 46XY Japanese female patient was clinically diagnosed as having lipoid CAH based on her clinical history of adrenal crisis at birth and the low basal concentrations of cortisol, aldosterone, adrenal androgens and testosterone in serum. In vitro studies of testicular mitochondrial enzymes confirmed a specific impairment of cholesterol side chain cleavage (SCC) activity. However, in spite of the virtual reduction of SCC activity, the amounts of immunodetectable P450scc, adrenodoxin reductase, and adrenodoxin in testicular mitochondria were almost same as those of normal testis. Furthermore, the size of each protein was similar to that of normal testis. Enzymatic amplification of the complementary DNA encoding P450scc from the patient's testis RNA and its nucleotide analysis by direct sequencing revealed no mutation. These results indicate that defective P450scc is not the lesion in this patient, confirming a previous report showing no P450scc mutations in patients with lipoid CAH. The exact lesion causing lipoid CAH in this patient is currently unknown.
对一名日本患者脂质肾上腺增生（脂质先天性肾上腺皮质增生症，lipoid CAH）的分子基础进行了研究。一名46XY核型的日本女性患者，基于其出生时肾上腺危象的临床病史以及血清中皮质醇、醛固酮、肾上腺雄激素和睾酮的低基础浓度，临床上被诊断为脂质先天性肾上腺皮质增生症。对睾丸线粒体酶的体外研究证实了胆固醇侧链裂解（SCC）活性存在特异性损害。然而，尽管SCC活性实际上降低了，但睾丸线粒体中免疫可检测到的P450scc、肾上腺皮质铁氧化还原蛋白还原酶和肾上腺皮质铁氧化还原蛋白的量与正常睾丸几乎相同。此外，每种蛋白质的大小与正常睾丸相似。通过对患者睾丸RNA中编码P450scc的互补DNA进行酶促扩增，并通过直接测序对其核苷酸进行分析，未发现突变。这些结果表明，缺陷的P450scc不是该患者的病变，证实了先前一份报告中显示脂质先天性肾上腺皮质增生症患者不存在P450scc突变。目前尚不清楚该患者中导致脂质先天性肾上腺皮质增生症的确切病变。
