Background: Anti-Müllerian hormone (AMH) is produced by small growing ovarian follicles. It inhibits both FSH induced maturation of follicles as well as aromatase activity. Genetic variation of AMH signalling is associated with age at menopause and circulating oestradiol levels, i.e. AMH rs10407022 T>G (intragenic) and AMHR2 rs11170547 C>T (putative enhancer).
Objective and hypotheses: This present study aims to investigate the impact of the two SNPs on hormonal as well as morphologic parameters in healthy girls.
Method: Participants were recruited as part of two population-based cohort studies of healthy children and adolescents: The longitudinal part of The COPENHAGEN Puberty Study (83 girls, 737 examinations) and The Mother-Child Cohort (nested cohort including TAUS and MRI of the ovaries, n=121). Subjects were genotyped for SNPs using KASP assays and grouped according to pubertal stages (Tanners classification: B1/B2+3/B4+5). We assessed associations of the genotypes with circulating hormone levels (AMH, FSH, LH, oestradiol, inhibin B) and the number of ovarian follicles.
Results: AMH rs10407022 T>G was associated with AMH levels in prepubertal girls: TT (n=47) vs GT+GG (n=18), AMH median (range) 18 (849) vs 30 (650) pmol/l, P=0.038 (MannWhitney U). This was not reflected in the number of AMH producing follicles (adjusted for Tanner stages): MRI follicles ≤6 mm (Effect size estimate β −0.073, P=0.508) and TAUS follicles ≤4 mm (β −0.155, P=0.144). AMHR2 rs11170547 C>T was associated with inhibin B in mid-puberty (B2+3): CC (n=87) vs CT+TT (n=33), 41 (10125) vs 57 (26215) pg/ml, P<0.001. This was not reflected in the number of inhibin B producing follicles (adjusted for Tanner stages): MRI follicles ≥7 mm (β −0.067, P=0.505) and TAUS follicles ≥5 mm (β −0.089, P=0.393).
Conclusion: Genetic variation of AMH signalling affects serum levels of AMH and inhibin B in peripubertal girls. The effect could not be explained by the number of ovarian follicles implying a direct effect on expression of AMH (AMH rs10407022 T>G) as well as inhibin B (AMHR2 rs11170547 C>T).
01 - 03 Oct 2015
European Society for Paediatric Endocrinology