Association between GH receptor polymorphism (exon 3 deletion), serum IGF1, semen quality, and reproductive hormone levels in 838 healthy young men

Eur J Endocrinol. 2014 Mar 8;170(4):555-63. doi: 10.1530/EJE-13-0729. Print 2014 Apr.

Abstract

Introduction: GH activity may be involved in male reproductive function. A common genetic polymorphism in the gene encoding the GH receptor (GHR) results in deletion of the entire exon 3 sequence (GHRd3 isoform). The short GHRd3/d3 isoform seems more sensitive compared with full-length receptors (GHRfl/fl).

Aim: TO INVESTIGATE THE ASSOCIATIONS BETWEEN GH ACTIVITY, EVALUATED BY EXON 3 GHR POLYMORPHISM, AND SERUM IGF1 VS REPRODUCTIVE HORMONES, SEMEN QUALITY, AND PRE- AND POSTNATAL GROWTH IN HEALTHY YOUNG MALES (N=838, MEAN AGE: 19.4 years).

Results: Compared with GHRfl/fl homozygous individuals (n=467) GHRd3/d3 homozygous individuals (n=69) tended to have larger semen volume (3.2 (2.4-4.3) vs 3.6 (2.6-4.7) ml, P=0.053) and higher serum inhibin-B levels (208 pg/ml (158-257) vs 227 pg/ml (185-264), P=0.050). Semen quality, levels of gonadotropins, testosterone, estradiol, sex hormone-binding globulin, and IGF1 were not associated with GHRd3 genotype. A twofold increase in serum IGF1 was associated with a 13% (4-23) increase in calculated free testosterone (P=0.004). By contrast IGF1 was inversely associated with serum inhibin-B (P=0.027), but showed no associations to semen quality. GHR genotype and serum IGF1 were not associated with size at birth or final height.

Conclusions: GHRd3 polymorphism seemed only to have a weak influence on male reproductive function of borderline significance. The sensitive GHRd3/d3 genotype may slightly increase testicular function, as evaluated by semen volume and levels of inhibin-B, but does not seem to influence Leydig cell steroidogenesis. GHR genotype did not influence pre- and postnatal growth.

MeSH terms

  • Adolescent
  • Base Sequence*
  • Carrier Proteins / genetics*
  • Estradiol / blood
  • Exons / genetics
  • Genotype
  • Gonadotropins / blood
  • Homozygote
  • Humans
  • Inhibin-beta Subunits / blood
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Polymorphism, Genetic
  • Semen Analysis*
  • Sequence Deletion*
  • Sex Hormone-Binding Globulin / metabolism
  • Testosterone / blood
  • Young Adult

Substances

  • Carrier Proteins
  • Gonadotropins
  • IGF1 protein, human
  • Sex Hormone-Binding Globulin
  • Testosterone
  • Estradiol
  • Insulin-Like Growth Factor I
  • Inhibin-beta Subunits
  • somatotropin-binding protein