Waldhauser F, Boepple P A, Schemper M, Mansfield M J, Crowley W F
Department of Pediatrics, University of Vienna, Austria.
J Clin Endocrinol Metab. 1991 Oct;73(4):793-6. doi: 10.1210/jcem-73-4-793.
In children a progressive decrease in nocturnal serum melatonin (MT) has been shown with advancing age, suggesting a reduction in the amplitude of the circadian MT curve with maturation. Whether this alteration of MT levels is related to human sexual maturation or occurs independently remains to be elucidated. Also, the impact of gonadal steroids on the MT rhythm remains an open question. We examined 56 patients (51 females and 5 males) with central precocious puberty (52 idiopathic and 4 neurogenic). Patients were studied before and 3, 6, and 12 months after initiation of GnRH analog treatment. Three hundred and thirty-seven endocrinologically normal subjects (190 males and 147 females) served as controls. In all subjects nocturnal serum MT (blood collection between 2300 and 0100 h) was measured with a highly specific RIA. In young patients, aged 1-5 yr, we found significantly lower MT levels than in age-matched controls. Pubertal patients, aged 5-9 yr, displayed nocturnal MT levels in the same range as control subjects approaching normal pubertal age. In contrast to endocrinologically normal children, there was no age-dependent decrease in nocturnal MT in untreated precocious puberty; rather, it appeared that serum MT had already declined in association with the onset of sexual maturation. Although there was a significant difference in weight between patients and age-matched controls, the low MT values in patients 1-5 yr old were only partly explained by the weight difference (P less than 0.0009); their pubertal status also contributed significantly (P less than 0.006). Pituitary-gonadal suppression induced by long term GnRH analog treatment did not result in a return to prepubertal MT levels; rather, nocturnal MT decreased during therapy. The collected data indicate that nocturnal serum MT levels are related to sexual maturation, since serum MT is similar in precocious puberty and normal pubertal children. Since suppression of the pituitary-gonadal axis did not result in increases in nocturnal MT levels in young patients with precocity (i.e. return to age-appropriate levels), the reduction of nocturnal MT with normal puberty is not likely to be dependent on pubertal gonadotropin or sex steroid milieu.
研究表明，随着年龄增长，儿童夜间血清褪黑素（MT）水平逐渐下降，这表明随着成熟，昼夜MT曲线的振幅减小。MT水平的这种变化是与人类性成熟相关还是独立发生，仍有待阐明。此外，性腺类固醇对MT节律的影响仍是一个悬而未决的问题。我们研究了56例中枢性性早熟患者（51例女性和5例男性）（52例特发性和4例神经源性）。在开始GnRH类似物治疗前以及治疗后3、6和12个月对患者进行了研究。337名内分泌正常的受试者（190名男性和147名女性）作为对照。在所有受试者中，均采用高特异性放射免疫分析法（RIA）测定夜间血清MT（于23:00至01:00之间采集血样）。在1 - 5岁的年轻患者中，我们发现其MT水平显著低于年龄匹配的对照组。5 - 9岁的青春期患者夜间MT水平与接近正常青春期年龄的对照受试者处于相同范围。与内分泌正常的儿童不同，未经治疗的性早熟患者夜间MT没有随年龄下降；相反，似乎血清MT已经随着性成熟的开始而下降。尽管患者与年龄匹配的对照组在体重上存在显著差异，但1 - 5岁患者的低MT值仅部分由体重差异解释（P < 0.0009）；他们的青春期状态也有显著影响（P < 0.006）。长期GnRH类似物治疗引起的垂体 - 性腺抑制并未导致MT水平恢复到青春期前水平；相反，治疗期间夜间MT下降。收集的数据表明，夜间血清MT水平与性成熟有关，因为性早熟儿童和正常青春期儿童的血清MT相似。由于抑制垂体 - 性腺轴并未导致早熟年轻患者夜间MT水平升高（即恢复到适合年龄的水平），正常青春期夜间MT的降低不太可能依赖于青春期促性腺激素或性类固醇环境。
