Department of Growth and Reproduction GR, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Rigshospitalet Section 5064, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Eur J Endocrinol. 2014 Mar 8;170(4):555-63. doi: 10.1530/EJE-13-0729. Print 2014 Apr.
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).
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).
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.
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.
生长激素(GH)的活性可能参与了男性的生殖功能。GH 受体(GHR)基因编码区的一个常见遗传多态性导致整个外显子 3 序列缺失(GHRd3 同工型)。与全长受体(GHRfl/fl)相比,短的 GHRd3/d3 同工型似乎更敏感。
研究通过外显子 3 GHR 多态性评估的 GH 活性与 IGF1 与生殖激素、精液质量以及健康年轻男性的产前和产后生长之间的关系(N=838,平均年龄 19.4 岁)。
与 GHRfl/fl 纯合子个体(n=467)相比,GHRd3/d3 纯合子个体(n=69)的精液量更大(3.2(2.4-4.3)比 3.6(2.6-4.7)ml,P=0.053),血清抑制素-B 水平更高(208pg/ml(158-257)比 227pg/ml(185-264),P=0.050)。精液质量、促性腺激素、睾酮、雌二醇、性激素结合球蛋白和 IGF1 与 GHRd3 基因型无关。血清 IGF1 增加两倍与计算得出的游离睾酮增加 13%(4-23)相关(P=0.004)。相比之下,IGF1 与血清抑制素-B 呈负相关(P=0.027),但与精液质量无关。GHR 基因型和血清 IGF1 与出生时的大小或最终身高无关。
GHRd3 多态性似乎仅对男性生殖功能有微弱影响,且具有统计学意义。敏感的 GHRd3/d3 基因型可能略微增加睾丸功能,如精液量和抑制素-B 水平所示,但似乎不影响睾丸间质细胞的类固醇生成。GHR 基因型不影响产前和产后的生长。