Changes in dimeric inhibin A and B during normal early puberty in boys and girls

OBJECTIVE Although recently developed specific and sensitive assays of bioactive dimeric inhibin A and B have given new insights into the pituitary-gonadal axis in adult men and during the adult female menstrual cycle, there have been no reports on circulating inhibin A and B during normal human puberty. The aim of this study was to assess the relationship of dimeric inhibin A and B to pubertal stage, FSH and testosterone or oestradiol in late prepuberty and in early puberty. STUDY DESIGN AND SUBJECTS Serial samples were collected during a prospective longitudinal trial of GH treatment in short normal children. Seven boys were studied from late prepuberty to genital stage 3, and six pre-menarche girls from late prepuberty to breast stage 4, MEASUREMENTS Dimeric inhibin A (girls only) and inhibin B (boys and girls) were measured by highly specific and sensitive two-site ELISAs, FSH by IRMA, testosterone and oestradiol by RIA. RESULTS In boys, inhibin B increased progressively from pubertal stages 1 to 3 (ANOVA P < 0.0001) and correlated strongly with mean testicular volume (r = 0.72, P = 0.0005). Prepubertal boys showed a positive correlation between inhibin B and FSH (r = 0.65, P = 0.056), whereas pubertal boys gave a strong negative correlation (r = 0.75, P = 0.012). In both prepubertal and pubertal boys positive correlations were observed between inhibin B (y) and testosterone (x) (r = 0.81, P = 0.008 and r = 0.62, P = 0.054 respectively), but the slope of the regression line between the two was much steeper before than after the onset of clinical puberty, In girls, both inhibin A and B increased through pubertal stages 1-4 (ANOVA P = 0.01 and P = 0.047 respectively), Both showed strong positive correlations with oestradiol (r = 0.80 and 0.79, P = 0.001) and with FSH (r = 0.83, P = 0.0004 and r = 0.80, P = 0.001), Inhibin A and B were also strongly correlated with each other (r = 0.92, P = 0.0001). CONCLUSIONS In boys, testicular production of inhibin B increases as puberty progresses. Our results show for the first time that the initiation of puberty is accompanied by a dramatic switch from a positive to a negative relation between inhibin B and FSH as inhibin B begins to exert the expected negative feedback on FSH. The results in girls suggest that, prior to menarche, the ovarian follicles produce inhibin A and B in strict proportion, and in progressively greater amounts as puberty proceeds, Measurement of dimeric inhibin A and B may provide a sensitive new tool for determining gonadal maturity in late prepuberty and early puberty.