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.


METHODS
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.


METHODS
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.
Crofton
P M
PM
Department of Paediatric Biochemistry, Royal Hospital for Sick Children, Edinburgh, UK.
Illingworth
P J
PJ
Groome
N P
NP
Stirling
H F
HF
Swanston
I
I
Gow
S
S
Wu
F C
FC
McNeilly
A
A
Kelnar
C J
CJ
D000293:Adolescent; D002648:Child; D019281:Dimerization; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006130:Growth Disorders / Q000188:drug therapy; D019382:Human Growth Hormone / Q000627:therapeutic use; D006801:Humans; D007265:Inhibins / Q000097:blood*; D008297:Male; D010455:Peptides / Q000097:blood; D011446:Prospective Studies; D029584:Prostatic Secretory Proteins; D011627:Puberty / Q000097:blood*; D012044:Regression Analysis; D013739:Testosterone / Q000097:blood
D010455:Peptides; D029584:Prostatic Secretory Proteins; C043076:beta-microseminoprotein; C094377:inhibin-alpha subunit; D019382:Human Growth Hormone; D013739:Testosterone; D004958:Estradiol; D007265:Inhibins; D005640:Follicle Stimulating Hormone