ESPE Abstracts (2015) 84 P-2-497

Genetic Variation in the FSH Signalling Pathway Affects Female Reproductive Hormones During Infancy

Louise S Henriksen, Casper P Hagen, Maria Assens, Kristian Almstrup & Katharina M Main


Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark


Background: Studies have shown that genetic variations in the FSH pathway (SNPs: FSHB −211G>T, FSHR −29G>A, and FSHR 2039A>G) affect peripubertal levels of serum FSH and age at pubertal onset in girls.

Objective and hypotheses: Genetic variations in the FSH pathway reflect circulating levels of female reproductive hormones during the postnatal gonadotropin surge.

Method: Blood samples were taken in girls of the Copenhagen Mother-Child Cohort at the age of 3 months and reproductive hormones measured by immunoassays. 235 girls were genotyped for FSH SNPs using KASP assays. Differences in hormone levels between genotypes were analysed with Kruskal-Wallis test.

Results: Girls homozygous for the minor allele FSHR -29AA showed a significantly lower level of serum FSH (median 3.1 IU/l) compared to the more common variants GG and GA (medians 4.1 and 3.5 respectively), P=0.016. Lower circulating oestradiol was observed in homozygous carriers of the minor allele FSHR 2039GG (median 23.5 pmol/l) compared to carriers of AA and AG (medians 31.0 and 33.0 respectively), P=0.052. No significant associations were found with LH, SHBG, inhibin A, and inhibin B.

Conclusion: As expected, reduced FSHR transduction (FSHR 2039GG) was associated with lower oestradiol levels. We were puzzled to find a negative association of FSHR −29 minor allele with FSH levels. Whether this reflects immature regulation of the HPG axis during the neonatal gonadotropin surge remains to be elucidated.

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