Grino P B, Isidro-Gutierrez R F, Griffin J E, Wilson J D
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8857.
J Clin Endocrinol Metab. 1989 Mar;68(3):578-84. doi: 10.1210/jcem-68-3-578.
A 46,XY infant with perineoscrotal hypospadias and microphallus was identified in a family in which seven individuals have severe hypospadias that is inherited in a pattern compatible with an X-linked defect. The infant had small testes that were palpable in the labioscrotal folds, the proximal urethra was male in character, and there was no vagina. Serum testosterone rose from 0.5 to 5.1 nmol/L in response to hCG, and there was a negligible clinical response to a short term course of testosterone enanthate. A clinical diagnosis of male pseudohermaphroditism due to androgen resistance was made. Studies in cultured genital skin fibroblasts disclosed normal 5 alpha-reductase activity, a normal amount of high affinity dihydrotestosterone binding, and normal up-regulation of androgen receptors when monolayers were incubated with dihydrotestosterone or mibolerone. Fibroblast cytosol preparations contained a normal 7-8S sedimenting peak of androgen binding. However, androgen binding in monolayers decreased 60% when the assay temperature was raised from 30 to 41 C, and the dissociation rate of ligand from the receptor was enhanced 5-fold compared to the control value, establishing the diagnosis of androgen resistance due to a qualitative abnormality of the androgen receptor. Because of parental decision to raise the patient as a male, he was given two courses of high dose testosterone cypionate when he was 2.5 and 3.5 yr old (100 mg every 2 weeks for six doses). This treatment produced significant phallic growth, making it possible to undertake surgical correction of the hypospadias. We postulate that the impairment of androgen receptor function was overcome in part by the large dose of androgen.
在一个家族中发现了一名患有会阴阴囊型尿道下裂和小阴茎的46,XY婴儿，该家族中有7人患有严重尿道下裂，其遗传模式符合X连锁缺陷。该婴儿睾丸较小，可在阴唇阴囊皱襞中触及，近端尿道呈男性特征，且无阴道。血清睾酮在人绒毛膜促性腺激素刺激下从0.5 nmol/L升至5.1 nmol/L，而庚酸睾酮短期疗程的临床反应可忽略不计。临床诊断为雄激素抵抗所致的男性假两性畸形。对培养的生殖器皮肤成纤维细胞的研究显示，5α-还原酶活性正常，高亲和力二氢睾酮结合量正常，当单层细胞与二氢睾酮或米勃龙孵育时，雄激素受体的上调正常。成纤维细胞胞质溶胶制剂中雄激素结合的沉降峰为正常的7-8S。然而，当测定温度从30℃升至41℃时，单层细胞中的雄激素结合减少了60%，与对照值相比，配体从受体上的解离速率提高了5倍，从而确诊为雄激素受体定性异常所致的雄激素抵抗。由于父母决定将患者当作男性抚养，他在2.5岁和3.5岁时接受了两个疗程的高剂量环戊丙酸睾酮治疗（每2周100 mg，共6剂）。这种治疗使阴茎显著生长，从而有可能对尿道下裂进行手术矫正。我们推测，大剂量雄激素部分克服了雄激素受体功能的损害。
