Jukier L, Kaufman M, Pinsky L, Peterson R E
J Clin Endocrinol Metab. 1984 Oct;59(4):679-88. doi: 10.1210/jcem-59-4-679.
We studied a family in which three brothers were born with ambiguous genitalia and had poor virilization at puberty. One patient (II-5) required less surgery to repair his hypospadias and is lean, muscular, and hairy compared to his brothers (II-1, II-2). Their adult levels of plasma testosterone (T) range from 765-2250 ng/dl. The plasma T to 5 alpha-dihydrotestosterone (DHT) ratios were 29 (n = 5) in patient II-1, 25 (n = 2) in patient II-2, and 14 (n = 2) in patient II-5, compared to 12 +/- 3 (SD) in normal men. The mean urinary etiocholanolone to androsterone ratios were 1.9 (n = 2) in patient II-1, 2.0 in patient II-2, and 1.3 in patient II-5, compared to 0.87 +/- 0.34 in normal men. The mean urinary ratios of 5 beta-tetrahydrocorticosterone to 5 alpha-tetrahydrocorticosterone were 0.98 (n = 2) in patient II-1, 1.25 in patient II-2, and 0.71 in patient II-5, compared to 0.53 +/- 0.22 in normal men. Genital skin fibroblasts (GSF) from patient II-1 had unusually low 5 alpha-reductase (5 alpha-R) activity (0.3 pmol/mg protein X h; n = 6), but those of patient II-5, a normal brother (II-3), and a sister (II-4; with impaired development of sexual hair) had normal values of 6.5 (n = 2), 9 (n = 3), and 9 (n = 2) pmol/mg protein X h, respectively. The maximum specific DHT receptor-binding activity (Bmax) and the rate constant of dissociation (k) of DHT-receptor complexes in the GSF from each of these individuals were normal, but the apparent equilibrium dissociation constants (Kd) for DHT were 1.16 +/- 0.28 (n = 4) in II-1, 0.39 +/- 0.20 (n = 6) in the sister, and it was 0.19 +/- 0.09 (n = 3) in the unaffected brother and 0.22 +/- 0.09 nM (n = 26) in normal men. The Bmax with the synthetic, nonmetabolizable androgen, methyltrienolone (R1881), and the k of R1881-receptor complexes were normal, but the Kd for R1881 in the GSF of II-1 was 1.4 nM (n = 2), compared to 0.16 +/- 0.05 (n = 8) in normal men, and prolonged exposure to R1881 failed to augment (up-regulate) the basal R1881-binding activity in his cells.(ABSTRACT TRUNCATED AT 400 WORDS)
我们研究了一个家族，该家族中有三兄弟出生时生殖器模糊，青春期男性化不足。其中一名患者（II - 5）修复尿道下裂所需的手术较少，与他的兄弟（II - 1、II - 2）相比，他身材瘦、肌肉发达且多毛。他们成年后的血浆睾酮（T）水平在765 - 2250 ng/dl之间。患者II - 1的血浆T与5α - 双氢睾酮（DHT）的比值为29（n = 5），患者II - 2为25（n = 2），患者II - 5为14（n = 2），而正常男性的该比值为12±3（标准差）。患者II - 1的尿表雄酮与雄酮的平均比值为1.9（n = 2），患者II - 2为2.0，患者II - 5为1.3，正常男性的该比值为0.87±0.34。患者II - 1的尿5β - 四氢皮质酮与5α - 四氢皮质酮的平均比值为0.98（n = 2），患者II - 2为1.25，患者II - 5为0.71，正常男性的该比值为0.53±0.22。患者II - 1的生殖器皮肤成纤维细胞（GSF）的5α - 还原酶（5α - R）活性异常低（0.3 pmol/mg蛋白质×小时；n = 6），但患者II - 5、一名正常兄弟（II - 3）和一名姐妹（II - 4；性毛发育受损）的GSF的该活性分别为正常的6.5（n = 2）、9（n = 3）和9（n = 2）pmol/mg蛋白质×小时。这些个体的GSF中DHT受体结合活性的最大值（Bmax）和DHT - 受体复合物的解离速率常数（k）均正常，但II - 1中DHT的表观平衡解离常数（Kd）为1.16±0.28（n = 4），姐妹为0.39±0.20（n = 6），未受影响的兄弟为0.19±0.09（n = 3），正常男性为0.22±0.09 nM（n = 26）。用合成的、不可代谢的雄激素甲基三烯olone（R1881）检测时，Bmax和R1881 - 受体复合物的k正常，但II - 1的GSF中R1881的Kd为1.4 nM（n = 2），而正常男性为0.16±0.05（n = 8），并且长时间暴露于R1881未能增强（上调）其细胞中的基础R1881结合活性。（摘要截断于400字）
