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Does height and IGF-I determine pubertal timing in girls?
Emmie N Upners1,2, Alexander S Busch3,4, Kristian Almstrup3,4
1Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark. emmie.nicolina.upners.02@regionh.dk.
Insights
Pubertal timing in girls is linked to height and insulin-like growth factor-I (IGF-I) levels. Taller girls and those with higher IGF-I experienced earlier puberty, while shorter girls had later onset.
Area of Science:
- Pediatric Endocrinology
- Growth Hormone Axis
- Pubertal Development
Background:
- Pubertal timing is influenced by the growth hormone/insulin-like growth factor (GH/IGF) axis.
- Key IGF-regulating factors include pregnancy-associated plasma protein-A/A2 (PAPP-A/PAPP-A2) and stanniocalcin 2 (STC2).
Purpose of the Study:
- To investigate the association between height, IGF-I concentration, and genotypes of PAPPA, PAPPA2, and STC2 with the timing of female pubertal milestones.
- To determine if genetic variations in IGF-regulating factors influence pubertal onset.
Main Methods:
- Analysis of height, IGF-I levels, and genotypes in 1382 Danish girls.
- Inclusion of cohorts with tall stature (≥2 SD) and short stature (≤-2 SD).
- Assessment of pubertal milestones: thelarche (breast development) and menarche.
Main Results:
- Thelarche occurred significantly earlier in tall girls and later in short girls compared to normal-stature girls.
- Higher IGF-I levels were associated with earlier thelarche and menarche.
- No significant association was found between PAPPA, PAPPA2, or STC2 genotypes and age at thelarche or menarche, although PAPPA2 minor allele carriers were shorter.
Conclusions:
- Height and IGF-I levels, but not specific genotypes of PAPP-A, PAPP-A2, and STC2, are negatively associated with age at thelarche and menarche.
- Childhood growth and IGF-I levels may serve as biomarkers for predicting pubertal timing.
Background:
Pubertal timing is closely linked to growth regulated by the growth hormone/insulin-like factor (GH/IGF) axis that includes IGF-regulating factors such as pregnancy-associated plasma protein-A/A2 (PAPP-A/PAPP-A2) and stanniocalcin 2 (STC2). We investigated the association between height, IGF-I concentration, and PAPPA, PAPPA2, and STC2 genotypes on the timing of female pubertal milestones.
Methods:
Height, IGF-I, and genotypes were analyzed in 1382 Danish girls from the general population, 67 patients with tall stature (height ≥2 SD), and 124 patients with short stature (height ≤-2 SD). The main outcomes were breast stage and menarche.
Results:
Thelarche occurred significantly earlier in patients with tall stature (mean age 9.37 years [95% confidence interval (CI) 8.87-9.87]) and later in patients with short stature (11.07 years [95% CI 10.7-11.43]) compared with girls within the normal range (9.96 years [95% CI 9.85-10.07]) (p = 0.02 and p < 0.01, respectively). Girls with higher IGF-I levels experienced thelarche and menarche earlier compared with the rest of the cohort (p < 0.01). Genotypes were not associated with age at thelarche nor menarche, but the PAPPA2 minor allele carriers were shorter compared with major allele carriers, p = 0.03.
Conclusions:
Height and IGF-I, but not PAPP-A, PAPP-A2, and STC2 genotypes, were negatively associated with age at thelarche and menarche.
Impact:
Girls with tall and short stature enter puberty earlier and later compared with girls with normal height. Girls with higher insulin-growth factor-I in childhood enter puberty earlier. Pubertal timing is influenced by longitudinal growth and IGF-I levels earlier in childhood. Childhood growth and the levels of IGF-I in childhood may be biomarkers of pubertal timing.
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