部分雄激素不敏感综合征患者体内高剂量睾酮反应与临床、内分泌和分子异常的相关性
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廷塞洛DG，桑德斯PT，哈金斯MB，辛普森NB，爱德华兹CR，哈格里夫斯TB，吴前锋
部分雄激素不敏感综合征患者体内高剂量睾酮反应与临床、内分泌和分子异常的相关性
中国性(Oxf)。1997年4月,46(4):497 - 506。
- PubMed ID
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9196614 (在PubMed］
- 摘要
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目的:研究两名之前诊断为莱芬斯坦综合征的患者对激素水平、氮平衡和皮脂分泌的分级大剂量睾酮的反应，并试图将这些参数与他们雄激素受体的特性和雄激素受体基因突变联系起来。设计:通过对照氮摄入量与排出量的比较来确定氮平衡。测量额头上的皮脂排出量。在对照组(无治疗)和丙酸睾酮治疗期间对患者进行研究。血液样本被用作基因组DNA的来源和测量周围激素水平;雄激素受体结合使用生殖器皮肤成纤维细胞。患者:2例XY核型患者，外生殖器模糊，有睾丸血统问题，青少年时需要乳房切除术。正常男性控制的生育能力。测量:在睾酮治疗(1或5 mg/kg/天)前后研究氮平衡、皮脂排泄率和外周激素水平(睾酮、双氢睾酮、LH和FSH)。基因组DNA提取从外周血白细胞和雄激素受体基因区域的聚合酶链反应扩增使用特异性引物对。 Mobility of amplified DNA from patients was analysed on denaturing gradient acrylamide gels and fragments differing in mobility from those of normal controls were sequenced. Fibroblasts were cultured from scrotal skin biopsies and androgen receptor binding parameters, subcellular localization and up-regulation were determined. RESULTS: Testosterone therapy resulted in raised plasma testosterone, dihydrotestosterone and oestradiol in both patients. In patient 1 (lesser genital abnormality), LH was suppressed by 5 mg/kg/day testosterone to the upper limit of the normal range but FSH remained low normal. Both LH and FSH were suppressed by testosterone treatment in patient 2 (greater genital abnormality). Nitrogen retention was increased in both patients (4.2 and 3.0 g/24 h respectively); sebum excretion rate increased to normal in patient 1 but showed no change in patient 2. Mutations in the androgen receptor gene were identified in both patients. In patient 1 a single nucleotide change from adenosine to guanosine resulted in the substitution of glycine for glutamic acid at position 772 within the hormone binding domain of the receptor. In patient 2 a single nucleotide mutation from guanosine to adenosine resulted in the substitution of lysine for arginine at position 608 (exon 3) situated in the second zinc finger of the DNA binding domain. Both patients had a normal number of androgen binding sites in genital skin fibroblasts but those in patient 1 showed reduced binding affinity and rapid dissociation of receptor/ligand complexes while those in patient 2 showed defective nuclear localization. CONCLUSION: In patients with partial androgen insensitivity syndrome the type of androgen receptor mutation and responses to short-term androgen treatment can be correlated with the individual's potential to virilize. If there is a mutation in the androgen receptor DNA binding domain the patient may show little ability to virilize either spontaneously at puberty or after androgen treatment. Sebum excretion appears to be more discriminating than nitrogen balance or gonadotrophin suppression as an index of tissue response to androgens.