Gender and sexual maturation-dependent contrasts in the neuroregulation ofgrowth hormone secretion in prepubertal and late adolescent males and females - A general clinical research center-based study

Although numerous studies have delineated an impact of gender on the neuroe ndocrine control of GH secretion in the adult, few investigations have defi ned the nature and extent of sex differences before puberty. This deficit r eflects jointly the sensitivity limitations of earlier GH assays and the pa ucity of intensive sampling protocols in healthy children. Here we have app lied a chemiluminescence-based GH assay (sensitivity, 0.005 mu g/L) to stud y GH release in blood sampled every 10 min for 12 h from 1800-0600 h in 58 healthy children. Males and females were evaluated in prepuberty (n = 17 bo ys; n = 11 girls) and late adolescence (n = 13 males; n = 17 females). We q uantitated the principal regulated facets of GH release by 1) deconvolution analysis to assess basal vs. pulsatile GH secretion, 2) approximate entrop y to compute the regularity of GH release patterns, and 3) cosine regressio n analysis to evaluate the overnight rhythmic release of GH. Gender by matu ration analysis of variance revealed a mean 2.3-fold increase in the integr ated serum GH concentration between prepuberty and late adolescence (P < 10 (-6)). Deconvolution analysis disclosed that 91-97% of total GH secretion w as pulsatile. Pulsatile, but not basal, GH release showed marked sexual mat uration dependence (P < 10(-5)). Pulsatile GH release rose in adolescents d ue to a 2.25-fold greater GH secretory burst mass (P = 0.00011), which refl ected joint 1.6-fold increases in GH secretory pulse amplitude and duration (P < 0.01). Pulse-mass enhancement across puberty was gender independent, but mechanistically specific, as GH pulse frequency, intersecretory burst i nterval, and half-life were invariant of pubertal status. The approximate e ntropy statistic identified more disorderly GH secretion patterns in adoles cent females compared with prepubertal children and adolescent males (P = 0 .00074). Cosinor analysis unmasked elevated overnight rhythms in GH secreto ry burst mass and interburst intervals in late adolescents of both genders compared with prepubertal boys (for burst mass) or girls (for interburst in tervals). Linear regression analysis disclosed strong correlations among 1) the plasma insulin-like growth factor I concentration and GH secretory bur st mass (P < 10(-3)), 2) the GH pulse mass and the serum testosterone conce ntration (P = 10-3), 3) the irregularity (entropy) of GH secretory patterns and the serum estradiol concentration (P < 10(-4)), and 4) the basal GH se cretion rate and the serum estradiol concentration (P = 10(-2)). In summary, healthy prepubertal children and late adolescent boys and girls manifest distinctive mechanisms controlling GH release, as appraised for a ll three of the pulsatile, entropic, and 12-h rhythmic modes of GH neuroreg ulation. The major maturational contrast in the pulsatile mode of GH secret ion is amplified secretory burst mass in adolescents due to jointly heighte ned GH pulse amplitude and duration. The dominant gender distinction lies i n the reduced orderliness of GH release patterns in late adolescent girls. Overnight rhythms in GH secretory burst mass and interburst intervals enlar ge in both sexes at adolescence, thus signaling enhanced coupling between t he rhythmic and pulsatile control of GH release at this time. At the extrem a of pubertal development, sex steroid hormones are associated differential ly with specific facets of GH release, e.g. an elevated basal GH secretion rate (estrogen), greater irregularity of GH release patterns (estrogen), an d amplified GH secretory burst mass and higher plasma insulin-like growth f actor I concentrations (testosterone). Accordingly, we postulate that sex s teroids supervise selectively each of the dominant facets of GH neurosecret ory control across human puberty.