Dimeric inhibins in girls from birth to adulthood: relationship with age, pubertal stage, FSH and oestradiol.

Abstract

Inhibin B is produced by granulosa cells in small antral follicles under the influence of FSH, whilst inhibin A is produced by larger follicles and the corpus luteum. The aims of our study were to investigate how these inhibins change from birth to late adolescence in girls, to derive reference data and to explore their relation with pubertal stage, FSH, oestradiol and each other. Blood samples were collected from: (a) 345 girls aged 0--18 years to obtain age-related reference data, and (b) 80 pre-menarcheal girls with full pubertal staging, of whom 40 were on GH treatment at the time of sampling. Dimeric inhibins A and B were measured by double antibody enzyme-linked immunosorbent assay (ELISA), FSH by immunoradiometric assay (IRMA) and oestradiol by radioimmunoassay. Median inhibin B was low until age 6 years, slightly higher from 6 to 10 years, then increased from 10 to 12 years to reach a plateau from 12 to 18 years. Inhibin A was usually detectable in girls younger than 3 months but thereafter became undetectable in most samples until after age 10 years, when median levels rose progressively to 14 years, then stabilized from 14 to 18 years. Both inhibins displayed considerable scatter about the median throughout infancy, childhood and adolescence. Girls aged 0--10 years showed a positive correlation between inhibins A and B (P < 0.0001), whereas those aged 14--18 years showed an inverse relationship (P < 0.001), indicating the onset of ovulatory cycles. Age-related reference ranges and data for calculation of SD scores are presented. GH-treated girls at pubertal stage B2 (but not at B1 or B3--5) had higher inhibin B and FSH levels than untreated girls and were excluded from further analysis. Both inhibins A and B increased during puberty (P < 0.0001) and were positively correlated with each other (P < 0.01). Both inhibins were also positively correlated with FSH in pre-pubertal girls (P < 0.05) but not at pubertal stages B3--5. Although median levels of inhibins A and B remained low until after age 10 years in girls, the increased levels of both inhibins in individual samples, together with their positive relationship with FSH, provide further evidence of sporadic follicular development throughout infancy and childhood under the influence of FSH. The increase in both inhibins during puberty and their changing relationship with FSH are in keeping with the concept of follicular growth being dependent on the duration of FSH elevation above a critical threshold rather than the degree of elevation per se.