Manasco P K, Girton M E, Diggs R L, Doppman J L, Feuillan P P, Barnes K M, Cutler G B, Loriaux D L, Albertson B D
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892.
N Engl J Med. 1991 Jan 24;324(4):227-31. doi: 10.1056/NEJM199101243240404.
Familial male precocious puberty is a gonadotropin-independent form of precocious puberty that occurs only in males. The cause of the disorder is unknown. To examine the hypothesis that the plasma of boys with familial male precocious puberty contains a novel stimulator of testicular testosterone production, we developed a bioassay using adult male cynomolgus monkeys.
We collected plasma from 12 boys with familial male precocious puberty, 7 normal prepubertal boys of similar ages and with similar plasma gonadotropin levels, and 1 boy with hypogonadotropic hypogonadism and infused it into the testicular artery of adult male cynomolgus monkeys that had been pretreated with gonadotropin-releasing-hormone antagonist to inhibit the endogenous secretion of gonadotropins. Testicular venous effluent was collected at 15-minute intervals for 3 or 5 hours for the measurement of testosterone.
The mean (+/- SE) peak testosterone response, as compared with base line, was significantly greater in the monkeys infused with plasma from the 12 boys with familial male precocious puberty than in the monkeys infused with plasma from the 7 normal prepubertal boys and the boy with hypogonadotropic hypogonadism (385 +/- 51 vs. 184 +/- 25 percent, P less than 0.005) in the three-hour studies. Plasma from 92 percent of the boys with familial male precocious puberty and 12.5 percent of the normal prepubertal boys stimulated a response greater than 195 percent of base-line values. In the animals studied for five hours after receiving a second dose of antagonist, the mean peak testosterone response, as compared with base line, was significantly greater in the monkeys infused with plasma from three boys with familial male precocious puberty than in the monkeys infused with plasma from three normal prepubertal boys (363 +/- 81 vs. 115 +/- 6 percent, P less than 0.01). The mean area under the testosterone-response curve was significantly larger in the monkeys infused with plasma from the boys with familial male precocious puberty in the five-hour studies (154 +/- 34 vs. -58 +/- 10 percent, P less than 0.005), but not in the three-hour studies.
These findings support the presence of a circulating testis-stimulating factor in the plasma of boys with familial male precocious puberty. The production of such a factor would explain the biologic nature of the disorder.
家族性男性性早熟是一种仅发生于男性的促性腺激素非依赖性性早熟形式。该疾病的病因尚不清楚。为检验家族性男性性早熟男孩血浆中含有一种新型睾丸睾酮生成刺激物这一假说，我们利用成年雄性食蟹猴开发了一种生物测定法。
我们收集了12名家族性男性性早熟男孩、7名年龄相仿且血浆促性腺激素水平相似的正常青春期前男孩以及1名低促性腺激素性性腺功能减退男孩的血浆，并将其注入经促性腺激素释放激素拮抗剂预处理以抑制促性腺激素内源性分泌的成年雄性食蟹猴的睾丸动脉。每隔15分钟收集3或5小时的睾丸静脉流出液以测定睾酮。
在3小时的研究中，与基线相比，注入12名家族性男性性早熟男孩血浆的猴子的平均（±标准误）睾酮峰值反应显著高于注入7名正常青春期前男孩和低促性腺激素性性腺功能减退男孩血浆的猴子（385±51对184±25%，P<0.005）。92%的家族性男性性早熟男孩和12.5%的正常青春期前男孩的血浆刺激反应大于基线值的195%。在接受第二剂拮抗剂后研究5小时的动物中，与基线相比，注入3名家族性男性性早熟男孩血浆的猴子的平均睾酮峰值反应显著高于注入3名正常青春期前男孩血浆的猴子（363±81对115±6%，P<0.01）。在5小时的研究中，注入家族性男性性早熟男孩血浆的猴子的睾酮反应曲线下平均面积显著更大（154±34对-58±10%，P<0.005），但在3小时的研究中并非如此。
这些发现支持家族性男性性早熟男孩血浆中存在一种循环的睾丸刺激因子。这种因子的产生可以解释该疾病的生物学本质。
