Maturation of luteinizing hormone (gonadotropin-releasing hormone) secretion across puberty: evidence for altered regulation in obese peripubertal girls

Abstract

Context: Peripubertal obesity (body mass index-for-age >or= 95%) in girls is associated with hyperandrogenemia. LH likely contributes to this relationship, but overnight LH secretion in obese girls is poorly characterized.

Objective: The aim of the study was to evaluate LH pulse characteristics in obese girls throughout pubertal maturation.

Design: We conducted a cross-sectional analysis.

Setting: The study was performed in a general clinical research center.

Participants: Eight nonobese and five obese Tanner 1-2 girls participated, as well as 32 nonobese and 12 obese Tanner 3-5 girls.

Intervention: Blood samples were collected every 10 min overnight (from 1900 to 0700 h).

Main outcome measures: LH pulse frequency, amplitude, and mean LH were measured in three 4-h time blocks (block 1, 1900-2300 h; block 2, 2300-0300 h; and block 3, 0300-0700 h).

Results: Tanner stage 1-2 nonobese girls demonstrated nocturnal increases of LH frequency (P < 0.01, block 1 vs. 2) and mean LH (P < 0.05, block 1 vs. 2 and 3). Obese Tanner 1-2 girls had lower 12-h LH frequency and LH amplitude (P < 0.05 for both), with no overnight changes of LH pulse parameters. Compared to normal, LH frequency was elevated in Tanner 3-5 obese girls (P < 0.01 in all blocks), whereas LH amplitude was low (P < 0.05 in all blocks). Overnight increases of LH amplitude were observed in nonobese Tanner 3-5 girls (P < 0.0001), but not in obese Tanner 3-5 girls.

Conclusions: Obesity in prepubertal and early pubertal girls is associated with reduced LH secretion and reduced nocturnal changes of LH. In later pubertal girls, obesity is linked with reduced LH amplitude, but elevated LH frequency; the latter may reflect effects of hyperandrogenemia.

Figure 1

Late evening and overnight LH characteristics in obese (solid circles) and nonobese (open squares) peripubertal girls stratified by Tanner breast stage. Data are presented as mean ± sem. The numbers of subjects in each group are shown below the Tanner stage labels. NO, Nonobese; OB, obese. For reference, data for obese Tanner 5 girls with PCOS (solid triangles) and without PCOS (open triangles) are shown separately in the last column.

Figure 2

Late evening and overnight gonadotropin characteristics in obese (solid circles) and nonobese (open squares) peripubertal girls stratified by Tanner breast stage grouping. Data are presented as mean ± sem. The numbers of subjects in each group are shown below the Tanner stage labels. NO, Nonobese; OB, obese. a, P < 0.05 vs. baseline (1900–2300 h); b, P < 0.01 vs. baseline (1900–2300 h); *, P < 0.05 vs. nonobese in the same time block; **, P < 0.01 vs. nonobese in the same time block. For reference, data for obese Tanner 5 girls with PCOS (solid triangles) and without PCOS (open triangles) are shown separately in the last column.

Figure 3

Late evening and overnight sex steroid concentrations in obese (solid circles) and nonobese (open squares) peripubertal girls stratified by Tanner breast stage. Data are presented as mean ± sem. Four-hour mean values (using data points bounded by the shaded areas) were used for statistical comparisons. For reference, data for obese Tanner 5 girls with PCOS (solid triangles) and without PCOS (open triangles) are shown separately in the last column. To convert from conventional to SI units: P × 3.18 (pmol/liter); free T × 3.467 (pmol/liter); E₂ × 3.671 (pmol/liter).