title: Association between GH receptor polymorphism (exon 3 deletion), serum IGF1, semen quality, and reproductive hormone levels in 838 healthy young men.
abstract: BACKGROUND
  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).
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Growth and Reproduction GR, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Rigshospitalet Section 5064, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Andreassen
authors.forename: R B
authors.initials: RB
authors.lastname: Jensen
authors.forename: N
authors.initials: N
authors.lastname: Jørgensen
authors.forename: A
authors.initials: A
authors.lastname: Juul
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D004958:Estradiol / Q000097:blood; D005091:Exons / Q000235:genetics; D005838:Genotype; D006062:Gonadotropins / Q000097:blood; D006720:Homozygote; D006801:Humans; D028322:Inhibin-beta Subunits / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D011110:Polymorphism, Genetic; D055101:Semen Analysis; D017384:Sequence Deletion; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D006062:Gonadotropins; C583557:IGF1 protein, human; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D028322:Inhibin-beta Subunits; C051815:somatotropin-binding protein