title: Effects of the FSH-β-subunit promoter polymorphism -211G->T on the hypothalamic-pituitary-ovarian axis in normally cycling women indicate a gender-specific regulation of gonadotropin secretion.
abstract: BACKGROUND
  A polymorphism in the FSHB promoter (-211G→T, rs10835638) was found to be associated with decreased FSH, elevated LH, reduced testosterone, and oligozoospermia in males. Although FSH is pivotal for ovarian function, no data on consequences of FSHB -211G→T are available in females.
  
  
  OBJECTIVE
  We studied the effects of FSHB -211G→T on the hypothalamic-pituitary-ovarian axis in women.
  
  
  METHODS
  In a university-based in vitro fertilization unit, women undergoing standardized diagnostics were genotyped and compared with a fertile control group.
  
  
  METHODS
  The study group consisted of 365 thoroughly characterized women with normal menstrual cycle intervals and proven ovulation, with predominantly male-factor infertility. The independently recruited control group included 438 women with proven fertility and no history of abortions.
  
  
  METHODS
  Distribution of alleles and genotypes were compared between the study group and controls. In the study group, associations of endocrine parameters with FSHB -211G→T were assessed.
  
  
  RESULTS
  Allele and genotype frequencies were not significantly different between the study population and controls (T-allele: 14.4 vs. 16.6%; TT-homozygotes: 2.5 vs. 3.2%). The FSHB -211G→T TT-genotype was strongly associated with elevated FSH (TT-homozygosity effect 2.05 U/liter, P = 0.003). LH increased with the number of T-alleles (1.30 U/liter per T-allele, P < 0.001). Additionally, FSHB -211G→T was associated with reduced progesterone (-1.96 ng/ml per T-allele, P = 0.047).
  
  
  CONCLUSIONS
  This is a report on phenotypic consequences of FSHB -211G→T on the hypothalamic-pituitary-ovarian axis in women. The findings, partially contradictory to those in men, point to a gender-specific compensatory mechanism of gonadotropin secretion, probably involving progesterone.
authors.affiliation: Department of Gynecology and Obstetrics, University Clinics of Münster, D-48149 Münster, Germany. Andreas.Schuering@ukmuenster.de
authors.forename: Andreas N
authors.initials: AN
authors.lastname: Schüring
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Busch
authors.forename: Nadja
authors.initials: N
authors.lastname: Bogdanova
authors.forename: Jörg
authors.initials: J
authors.lastname: Gromoll
authors.forename: Frank
authors.initials: F
authors.lastname: Tüttelmann
mesh_terms: D016022:Case-Control Studies; D005260:Female; D037201:Follicle Stimulating Hormone, beta Subunit / Q000235:genetics*; D005787:Gene Frequency; D006062:Gonadotropins / Q000378:metabolism*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000502:physiology*; D007246:Infertility / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008597:Menstrual Cycle / Q000235:genetics / Q000502:physiology; D010053:Ovary / Q000378:metabolism / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D055571:Secretory Pathway / Q000235:genetics / Q000502:physiology; D012727:Sex Characteristics
chemical_list: D037201:Follicle Stimulating Hormone, beta Subunit; D006062:Gonadotropins