title: Genetically determined dosage of follicle-stimulating hormone (FSH) affects male reproductive parameters.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Human Molecular Genetics Research Group, Institute of Molecular and Cell Biology, University of Tartu, 51010 Tartu, Estonia.
authors: Marina
authors: M
authors: Grigorova
authors: Margus
authors: M
authors: Punab
authors: Birutė
authors: B
authors: Zilaitienė
authors: Juris
authors: J
authors: Erenpreiss
authors: Kristo
authors: K
authors: Ausmees
authors: Valentinas
authors: V
authors: Matuleviĉius
authors: Igor
authors: I
authors: Tsarev
authors: Niels
authors: N
authors: Jørgensen
authors: Maris
authors: M
authors: Laan
mesh_terms: D000293:Adolescent; D000483:Alleles; D015992:Body Mass Index; D015331:Cohort Studies; D004958:Estradiol / Q000097:blood / Q000235:genetics; D005640:Follicle Stimulating Hormone / Q000235:genetics*; D018628:Gene Dosage; D006801:Humans; D007265:Inhibins / Q000097:blood / Q000235:genetics; D007986:Luteinizing Hormone / Q000097:blood / Q000235:genetics; D008297:Male; D009929:Organ Size / Q000235:genetics; D012098:Reproduction / Q000235:genetics*; D013081:Sperm Motility / Q000235:genetics; D013091:Spermatogenesis / Q000235:genetics; D013737:Testis / Q000033:anatomy & histology*; D013739:Testosterone / Q000097:blood / Q000235:genetics; D055815:Young Adult
chemical_list: C422364:inhibin B; D013739:Testosterone; D004958:Estradiol; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone