Human Molecular Genetics Research Group, Institute of Molecular and Cell Biology, University of Tartu, 51010 Tartu, Estonia.
J Clin Endocrinol Metab. 2011 Sep;96(9):E1534-41. doi: 10.1210/jc.2011-0632. Epub 2011 Jul 6.
The detailed role of FSH in contributing to male testicular function and fertility has been debated. We have previously identified the association between the T-allele of the FSHB promoter polymorphism (rs10835638; G/T, -211 bp from the mRNA start) and significantly reduced male serum FSH.
In the current study, the T-allele carriers of the FSHB -211 G/T single nucleotide polymorphism represented a natural model for documenting downstream phenotypic consequences of insufficient FSH action.
We genotyped rs10835638 in the population-based Baltic cohort of young men (n = 1054; GG carriers, n = 796; GT carriers, n = 244; TT carriers, n = 14) recruited by Andrology Centres in Tartu, Estonia; Riga, Latvia; and Kaunas, Lithuania. Marker-trait association testing was performed using linear regression (additive, recessive models) adjusted by age, body mass index, smoking, and recruitment center.
Serum hormones directly correlated with the T-allele dosage of rs10835638 included FSH (additive model, P = 1.11 × 10(-6); T-allele effect, -0.41 IU/liter), inhibin-B (P = 2.16 × 10(-3); T-allele effect, -14.67 pg/ml), and total testosterone (P = 9.30 × 10(-3); T-allele effect, -1.46 nmol/liter). Parameters altered only among TT homozygotes were reduced testicular volume (recessive model, P = 1.19 × 10(-4); TT genotype effect, -9.47 ml) and increased serum LH (P = 2.25 × 10(-2); TT genotype effect, 1.07 IU/liter). The carrier status of rs10835638 alternative genotypes did not affect sperm motility and morphology, calculated free testosterone, serum SHBG, and estradiol concentrations.
We showed for the first time that genetically determined low FSH may have wider downstream effects on the male reproductive system, including impaired testes development, altered testicular hormone levels (inhibin-B, total testosterone, LH), and affected male reproductive potential.
FSH 在促进男性睾丸功能和生育能力方面的详细作用一直存在争议。我们之前已经确定了 FSHB 启动子多态性（rs10835638；从 mRNA 起点的-211bp 处的 T 等位基因）与男性血清 FSH 显著降低之间的关联。
在本研究中，FSHB-211G/T 单核苷酸多态性的 T 等位基因携带者代表了记录 FSH 作用不足的下游表型后果的天然模型。
我们在爱沙尼亚塔尔图、拉脱维亚里加和立陶宛考纳斯的男科中心招募的基于人群的年轻男性巴尔蒂克队列中（n=1054；GG 携带者 n=796；GT 携带者 n=244；TT 携带者 n=14）对 rs10835638 进行了基因分型。使用线性回归（加性、隐性模型）对标记-性状关联进行检验，调整因素为年龄、体重指数、吸烟和招募中心。
与 rs10835638 的 T 等位基因剂量直接相关的血清激素包括 FSH（加性模型，P=1.11×10(-6)；T 等位基因效应，-0.41IU/l）、抑制素-B（P=2.16×10(-3)；T 等位基因效应，-14.67pg/ml）和总睾酮（P=9.30×10(-3)；T 等位基因效应，-1.46nmol/l）。仅在 TT 纯合子中改变的参数是睾丸体积减小（隐性模型，P=1.19×10(-4)；TT 基因型效应，-9.47ml）和血清 LH 升高（P=2.25×10(-2)；TT 基因型效应，1.07IU/l）。rs10835638 替代基因型的携带状态不影响精子活力和形态、计算游离睾酮、血清 SHBG 和雌二醇浓度。
我们首次表明，遗传决定的低 FSH 可能对男性生殖系统产生更广泛的下游影响，包括睾丸发育受损、睾丸激素水平改变（抑制素-B、总睾酮、LH）以及男性生殖潜能受损。
