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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

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CONTEXT: 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.

DESIGN AND SETTING: In a university-based in vitro fertilization unit, women undergoing standardized diagnostics were genotyped and compared with a fertile control group.

PATIENTS: 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.

MAIN OUTCOME MEASURES: 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.

Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Volume98
Issue number1
Pages (from-to)E82-6
ISSN0021-972X
DOIs
Publication statusPublished - Jan 2013
Externally publishedYes

    Research areas

  • Case-Control Studies, Female, Follicle Stimulating Hormone, beta Subunit, Gene Frequency, Gonadotropins, Humans, Hypothalamo-Hypophyseal System, Infertility, Male, Menstrual Cycle, Ovary, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Retrospective Studies, Secretory Pathway, Sex Characteristics, Journal Article, Research Support, Non-U.S. Gov't

ID: 50123686