Guercio Gabriela, Rivarola Marco A, Chaler Eduardo, Maceiras Mercedes, Belgorosky Alicia
Endocrinology Service, Garrahan Pediatric Hospital, Buenos Aires C1245AAM, Argentina.
J Clin Endocrinol Metab. 2002 Mar;87(3):1162-9. doi: 10.1210/jcem.87.3.8330.
In girls, but not in boys, pronounced adrenarche and precocious pubarche along with ovarian hyperandrogenism have been related to insulin resistance and reduced fetal growth. However, insulin secretion is increased during puberty in normal boys. The aim of this study was to analyze the possible implication of changes in the GH/IGF-I axis and in insulin sensitivity for the regulation of adrenal androgen secretion of normal prepubertal and adolescent boys. Fifty-six normal boys were divided into the following groups (Gr): Gr1, prepuberty (testicular volume, <4 cc; n = 33); and Gr3, puberty (testicular volume, 4-25 cc; n = 23). Gr1 was subdivided according to age into: Gr1A, early prepuberty (boys younger than 5.9 yr old; n = 16); and Gr1B, late prepuberty (prepubertal boys, 5.9 yr old or older; n = 17). Gr3 was subdivided according to testicular volume into: Gr3A, early puberty (testicular volume, 4-8 cc; n = 13); and Gr3B, late puberty (testicular volume, 10--25 cc; n = 10). To study hormonal changes during the transition between prepuberty and puberty, an additional group, Gr2 (n = 30), was defined by mixing Gr1B and Gr3A. Serum dehydroepiandrosterone sulfate (DHEAS), androstenedione (Delta(4)A), insulin, IGF-I, and glucose were determined after overnight fasting. Insulin sensitivity was estimated by the fasting glucose/insulin (G/I) ratio. There was a close correlation between fasting G/I ratio and QUICKI, a quantitative insulin sensitivity check index. Mean values for Gr1 and Gr3 as well as their subgroups were compared using t test. In Gr1, the mean fasting G/I ratio was significantly higher, and the mean serum IGF-I, serum DHEAS, and serum Delta(4)A levels were significantly lower than in Gr3 (P < 0.001). Mean fasting G/I ratios in Gr1A and Gr3A were not significantly different from those in Gr1B and Gr3B, respectively, but the fasting G/I ratio in Gr3A was significantly lower than that in Gr1B (P < 0006). Moreover, body mass index (BMI) in Gr3A was significantly higher than that in Gr1B (P < 0.01). On the other hand, mean serum IGF-I levels in Gr1A and Gr3A were significantly lower than those in Gr1B and Gr3B, respectively (P < 0.0001). The mean serum DHEAS level in Gr1A was significantly lower than that in Gr1B (P < 0.01), but no difference was found between Gr3A and Gr3B. The mean serum Delta(4)A in Gr1A was similar to that in Gr1B, but the mean serum Delta(4)A in Gr3A was significantly lower than that in Gr3B (P = 0.0001). Correlation studies within Gr1, Gr2, and Gr3 were also carried out. There was a significant positive correlation between serum DHEAS and age in Gr1 and Gr2, but not in Gr3. In Gr1, no significant correlation was found between serum DHEAS and fasting G/I ratio or between serum DHEAS and serum IGF-I, suggesting that adrenal steroidogenesis in male prepuberty is independent of insulin sensitivity or peripheral IGF-I. In Gr2, a significant negative correlation (P = 0.01) between serum DHEAS and the fasting G/I ratio was found, but not between serum DHEAS and serum IGF-I. Furthermore, a significant negative correlation between BMI and the fasting G/I ratio was also found. Therefore, changes in insulin sensitivity might be involved in adrenal androgen synthesis during the transition from prepuberty to puberty. Finally, in Gr3, DHEAS was not significantly correlated with the fasting G/I ratio or serum IGF-I. A significant negative correlation between serum Delta(4)A and the fasting G/I ratio was found in Gr2. In Gr2, but not in Gr3, there was a significant negative correlation between the fasting G/I ratio and age (P = 0.03) and between the fasting G/I ratio and serum IGF-I (P = 0.03). In conclusion, our data support the hypothesis that the GH/IGF-I axis and insulin sensitivity are not involved in the mechanism of adrenarche in boys. Insulin sensitivity and BMI, however, decrease at early puberty rather than at late puberty, and this change could be involved in modulating adrenal androgen steroidogenesis during the transition between late prepuberty and early puberty.
在女孩中，而非男孩中，明显的肾上腺初现和青春期阴毛早现以及卵巢雄激素过多与胰岛素抵抗和胎儿生长受限有关。然而，正常男孩在青春期胰岛素分泌会增加。本研究的目的是分析生长激素/胰岛素样生长因子 - I（GH/IGF - I）轴变化和胰岛素敏感性对正常青春期前及青春期男孩肾上腺雄激素分泌调节的可能影响。56名正常男孩被分为以下几组（Gr）：Gr1，青春期前（睾丸体积<4立方厘米；n = 33）；Gr3，青春期（睾丸体积4 - 25立方厘米；n = 23）。Gr1根据年龄进一步细分：Gr1A，青春期早期（年龄小于5.9岁的男孩；n = 16）；Gr1B，青春期晚期（5.9岁及以上的青春期前男孩；n = 17）。Gr3根据睾丸体积细分：Gr3A，青春期早期（睾丸体积4 - 8立方厘米；n = 13）；Gr3B，青春期晚期（睾丸体积10 - 25立方厘米；n = 10）。为研究青春期前到青春期过渡期间的激素变化，通过混合Gr1B和Gr3A定义了一个额外的组Gr2（n = 30）。过夜禁食后测定血清硫酸脱氢表雄酮（DHEAS）、雄烯二酮（Δ⁴A）、胰岛素、IGF - I和葡萄糖。通过空腹血糖/胰岛素（G/I）比值评估胰岛素敏感性。空腹G/I比值与定量胰岛素敏感性检查指数QUICKI密切相关。使用t检验比较Gr1和Gr3及其亚组的平均值。在Gr1中，平均空腹G/I比值显著更高，平均血清IGF - I、血清DHEAS和血清Δ⁴A水平显著低于Gr3（P < 0.001）。Gr1A和Gr3A的平均空腹G/I比值分别与Gr1B和Gr3B的无显著差异，但Gr3A的空腹G/I比值显著低于Gr1B（P < 0.006）。此外，Gr3A的体重指数（BMI）显著高于Gr1B（P < 0.01）。另一方面，Gr1A和Gr3A的平均血清IGF - I水平分别显著低于Gr1B和Gr3B（P < 0.0001）。Gr1A的平均血清DHEAS水平显著低于Gr1B（P < 0.01），但Gr3A和Gr3B之间未发现差异。Gr1A的平均血清Δ⁴A与Gr1B相似，但Gr3A的平均血清Δ⁴A显著低于Gr3B（P = 0.0001）。还在Gr1、Gr2和Gr3内进行了相关性研究。在Gr1和Gr2中，血清DHEAS与年龄呈显著正相关，但在Gr3中无此相关性。在Gr1中，血清DHEAS与空腹G/I比值或血清DHEAS与血清IGF - I之间未发现显著相关性，表明男性青春期前肾上腺类固醇生成独立于胰岛素敏感性或外周IGF - I。在Gr2中，发现血清DHEAS与空腹G/I比值之间存在显著负相关（P = 0.01），但血清DHEAS与血清IGF - I之间无此相关性。此外，BMI与空腹G/I比值之间也存在显著负相关。因此，从青春期前到青春期过渡期间，胰岛素敏感性变化可能参与肾上腺雄激素合成。最后，在Gr3中，DHEAS与空腹G/I比值或血清IGF - I无显著相关性。在Gr2中发现血清Δ⁴A与空腹G/I比值之间存在显著负相关。在Gr2中，而非Gr3中，空腹G/I比值与年龄（P = 0.03）以及空腹G/I比值与血清IGF - I（P = 0.03）之间存在显著负相关。总之，我们的数据支持以下假设：GH/IGF - I轴和胰岛素敏感性不参与男孩肾上腺初现机制。然而，胰岛素敏感性和BMI在青春期早期而非晚期降低，这种变化可能参与调节青春期晚期到青春期早期过渡期间的肾上腺雄激素类固醇生成。
