Relationship between the growth hormone/insulin-like growth factor-1 axis, insulin sensitivity and adrenal androgens in normal prepubertal and pubertal boys.

GUERCIO G,; RIVAROLA MA,; CHALER E,; MACEIRAS M,; BELGOROSKY, A

JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM

The Endocrine Society

Lugar: Chevy Chase; Año: 2002 vol. 87 p. 1162 - 1169

0021-972X

In girls, but not in boys, pronounced adrenarche and precociouspubarche along with ovarian hyperandrogenism havebeen related to insulin resistance and reduced fetal growth.However, insulin secretion is increased during puberty innormal boys. The aim of this study was to analyze the possibleimplication of changes in the GH/IGF-I axis and in insulinsensitivity for the regulation of adrenal androgen secretion ofnormal prepubertal and adolescent boys. Fifty-six normalboys 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 accordingto age into: Gr1A, early prepuberty (boys youngerthan 5.9 yr old;n
16); and Gr1B, late prepuberty (prepubertalboys, 5.9 yr old or older; n
17). Gr3 was subdivided accordingto 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 transitionbetween prepuberty and puberty, an additional group,Gr2 (n
30), was defined by mixing Gr1B and Gr3A. Serumdehydroepiandrosterone sulfate (DHEAS), androstenedione(4A), insulin, IGF-I, and glucose were determined after overnightfasting. Insulin sensitivity was estimated by the fastingglucose/insulin (G/I) ratio. There was a close correlation betweenfasting G/I ratio and QUICKI, a quantitative insulinsensitivity check index.Mean values for Gr1 and Gr3 as well as their subgroupswere compared using t test. In Gr1, the mean fasting G/I ratiowas significantly higher, and the mean serum IGF-I, serumDHEAS, and serum 4A levels were significantly lower than inGr3 (P<0.001). Mean fasting G/I ratios in Gr1A and Gr3A werenot significantly different from those in Gr1B and Gr3B, respectively,but the fasting G/I ratio in Gr3A was significantlylower 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 andGr3A were significantly lower than those in Gr1B and Gr3B,respectively (P < 0.0001). The mean serum DHEAS level inGr1A was significantly lower than that in Gr1B (P < 0.01), butno difference was found between Gr3A and Gr3B. The meanserum 4A in Gr1A was similar to that in Gr1B, but the meanserum 4A in Gr3A was significantly lower than that in Gr3B(P
0.0001).Correlation studies within Gr1, Gr2, and Gr3 were also carriedout. There was a significant positive correlation betweenserum DHEAS and age in Gr1 and Gr2, but not in Gr3. In Gr1,no significant correlation was found between serum DHEASand fasting G/I ratio or between serum DHEAS and serumIGF-I, suggesting that adrenal steroidogenesis in male prepubertyis independent of insulin sensitivity or peripheralIGF-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 thefasting G/I ratio was also found. Therefore, changes in insulinsensitivity might be involved in adrenal androgen synthesisduring the transition from prepuberty to puberty. Finally, inGr3, DHEAS was not significantly correlated with the fastingG/I ratio or serum IGF-I. A significant negative correlationbetween serum 4A and the fasting G/I ratio was found in Gr2.In Gr2, but not in Gr3, there was a significant negative correlationbetween the fasting G/I ratio and age (P
0.03) andbetween the fasting G/I ratio and serum IGF-I (P
0.03).In conclusion, our data support the hypothesis that theGH/IGF-I axis and insulin sensitivity are not involved in themechanism of adrenarche in boys. Insulin sensitivity andBMI, however, decrease at early puberty rather than at latepuberty, and this change could be involved in modulatingadrenal androgen steroidogenesis during the transition betweenlate prepuberty and early puberty. (J Clin EndocrinolMetab 87: 1162?1169, 2002