Endocrine Abstracts

Introduction: A common genetic polymorphism in the GH receptor (GHR) is deletion of the entire exon 3 sequence (GHRd3 isoform). The GHRd3 isoform seems to be more sensitive with increased downstream GH signalling in activated exon 3 deleted receptor dimers (GHRd3/d3) compared to full length receptor dimers (GHRfl/fl). Presence of the GHRd3 isoform might be associated to pre- and postnatal growth and pubertal development in boys, although controversy exists. The aim was to investigate the influence of exon 3 GHR polymorphism on pre- and postnatal growth, insulin-like growth factor 1 (IGF1) serum levels, IGF binding protein 3 (IGFBP-3) levels, reproductive hormone levels (gonadotropins, testosterone, estradiol, sex hormone binding globulin) and semen quality (semen volume, sperm counts, sperm motility and sperm morphology).

Method/design: Population-based study consisting of 838 healthy young males. Data on prenatal growth were available in 428 individuals.

Results: Corrected for gestational age there was a trend towards higher birth weight (standard deviation score) among GHRd3/d3 homozygotes (n=41) compared to GHRfl/f homozygotes (n=241) (0.55±1.6 vs 0.15±1.3, P=0.09). Final height (P=0.59), IGF1 levels (P=0.79) and IGFBP-3 levels (P=0.49) were not significantly associated with GHRd3 polymorphism.

GHRd3/d3 homozygotes (n=69) compared to GHRfl/fl homozygotes (n=467) had significantly larger semen volume (3.6 (2.6–4.7) vs 3.2 (2.4–4.3) ml, P=0.049) and higher serum inhibin-B levels (227 (185–264) vs 208 (158–257), P=0.052). Levels of other reproductive hormones and other variables reflecting semen quality were not significantly associated with the GHR genotype.

Conclusions: Presence of GHRd3/d3 genotype was weakly associated with increased testicular function as evaluated by semen volume and levels of inhibin-B but did not influence other reproductive hormone levels or semen quality. Serum IGF1 and pre- and postnatal growth were not significantly influenced by GHRd3 polymorphism.