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

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 (nZ838, mean age: 19.4 years). Results: Compared with GHRfl/fl homozygous individuals (nZ467) GHRd3/d3 homozygous individuals (nZ69) tended to have larger semen volume (3.2 (2.4-4.3) vs 3.6 (2.6-4.7) ml, PZ0.053) and higher serum inhibin-B levels (208 pg/ml (158-257) vs 227 pg/ml (185-264), PZ0.050). 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 (PZ0.004). By contrast IGF1 was inversely associated with serum inhibin-B (PZ0.027), 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.

Growth Hormone and Reproduction: A Review of Endocrine and Autocrine/Paracrine Interactions

“…In contrast, GH does not appear to enhance gametogenesis in many GH-replete animals, since GH supplementation does not alter germ cell apoptosis in bulls [ 91 ] nor sperm number in monkeys [ 63 ] and postpubertal rats [ 92 ]. Moreover, men with the GHR3d (3rd exon) deletion do not have improved semen quality or steroid production, despite the increased GH sensitivity conveyed by this mutation [ 93 ].…”

Testicular Growth and Pubertal Onset in GH-Deficient Children Treated With Growth Hormone: A Retrospective Study

“…Its serum levels are known to augment with the increase of TV in healthy children (27). Several previous studies have tried to understand if rhGH treatment may somehow improve sperm parameters in adulthood (28)(29)(30) or whether a relationship between IGF1 serum levels in adulthood and sperm parameters do exist (31). The results of these studies showed no effect, and, therefore, the idea that the GH-IGF1 may play a role in the reproductive system was abandoned.…”

Association of the GHRd3 polymorphism with adult height and type 2 diabetes in a Saudi Arabian population from Jazan Province: A case-control study

“…5,9 However, regardless of the large number of studies reporting the effect of the GHRd3 polymorphism on human growth under some conditions, the direct effect of the GHRd3 polymorphism on the final adult height in the general population remains to be investigated. The sensitive GHRd3 allele may also be associated with increased male reproductive function such as high semen quality and sex-hormones levels 10 and a decreased risk of breast cancer. 11 The GHRd3 polymorphism has also been implicated in the pathogenesis of insulin resistance and type-2 diabetes mellites (T2DM).…”