The exon 3 deleted growth hormone receptor gene is associated with small birth size and early pubertal onset in healthy boys.

CONTEXT: The GH/IGF-I axis influences gonadal development and function. Recently, a deletion of exon 3 in the GH receptor gene (GHRd3) has been linked to increased responsiveness to GH.
OBJECTIVE: Our objective was to evaluate the influence of the GHRd3 gene on birth size and pubertal onset. DESIGN AND
SETTING: We conducted a cross-sectional study, part of The COPENHAGEN Puberty Study, at a tertiary center for pediatric endocrinology. PARTICIPANTS: Participants included 618 healthy boys aged 6.1-19.8 yr. MAIN OUTCOME MEASURES: We assessed pubertal onset by genital staging and testicular palpation and parental reported birth weight and length. GHR genotypes were determined by multiplex PCR.
RESULTS: Age at onset of genital development (G2+) was significantly earlier in the GHRd3 homozygotes (GHRd3/d3) [10.86 (10.35-11.37) yr, mean (95% confidence interval)] compared with the full-length homozygotes (GHRfl/fl) [11.76 (11.35-12.00) yr, P = 0.002]. The odds ratio of having detectable testosterone levels for a given age was significantly higher in GHRd3/d3 compared with GHRfl/fl group (odds ratio = 3.1; 95% confidence interval = 1.2-8.9; P = 0.036). The GHRd3/d3 group the higher prepubertal IGF-I levels compared with the GHRfl/fl group (9.2% (0.1-18.1%), P = 0.048) after adjustment for IGF-binding protein-3 levels. Lower gestational-age-adjusted birth weight and length were found in the GHRd3/d3 group compared with the GHRfl/fl group and the GHRfl/d3 group, respectively (all P < or = 0.018).
CONCLUSION: The GHRd3/d3 genotype was associated with smaller birth size and earlier age at pubertal onset compared with the GHRfl/fl genotype. Thus, this common polymorphism could play a role for prenatal growth and gonadal development in boys.