Developmentally delimited emergence of more orderly luteinizing hormone and testosterone secretion during late prepuberty in boys

To quantitate changing feedback control in the GnRH-LH/FSH-testosterone axi s in male puberty, we here quantitate the orderliness of hormone release pa tterns using the regularity (pattern-sensitive) statistic, approximate entr opy (ApEn), in 46 eugonadal boys representing 6 genitally defined stages of normal puberty. ApEn is a single variable, model-free, and scale-independe nt barometer of coordinate signaling or integrative regulation within a cou pled neuroendocrine axis. Accordingly, we quantitated ApEn of LH profiles o btained by immunofluorometric assay of sera sampled every 20 min for 24 h. LH ApEn declined remarkably between early prepuberty (genital stage I-A: me an hone age, 4.6 +/- 1.6 yr; testis volume, <3 mL for at least 3 succeeding yr) and late prepuberty (genital stage I-C: bone age, 8.7 +/- 1.8 yr; test is volume, <3 mL for up to 1 yr thereafter; P = 0.00019), which indicates t he acquisition of more regular LH release patterns in late prepuberty. Maxi mal LH orderliness occurred in puberty stage II (bone age, 10.7 +/- 1.0 yr; testis volume, 2.8 +/- 0.4 mL). The LH secretory process was more disorder ly in mid- and Inter puberty (Tanner stages III and IV). Transpubertal vari ations in testosterone ApEn manifested a similar tempo, i.e. the greatest r egularity of testosterone secretion (lowest ApEn) emerged in Tanner genital stage II (P < 10(-7)), with less orderly patterns evident both earlier and later in sexual development. In contrast, FSH ApEn values remained invaria nt of pubertal status. Analysis of bihormonal coupling using the theoretica lly related bivariate cross-ApEn statistic disclosed maximal 2-hormone sync hrony for LK and testosterone secretion in genital stage II (P = 0.031), wi th relative deterioration of coordinate LH and testosterone release pattern s both before and after. LH and FSH release became maximally synchronous at the end of prepuberty (genital stage I-C; P = 0.029), and FSK and testoste rone synchrony peaked in pubertal stage III (P = 0.037). As mean 24-h serum concentrations of LK, FSH, and testosterone rose transpubertally by 35-fol d (LH), 68-fold (FSK), and 70-fold (testosterone), respectively, ive infer that pubertal developmental stage per se rather than level of hormone outpu t dictates coordinate GnRH-LH/FSH-testosterone secretion. In summary, in eugonadal boys, the regularity of 24-h LH and testosterone s ecretory patterns undergoes well defined pubertal stage-specific control. N o sexually developmentally delimited regulation is inferable for FSK. The c oncept of temporally biphasic puberty-dependent variations in neurohormone secretory regularity contrasts with the unidirectional rise in daily hormon e output. Accordingly, we infer that late prepuberty and early puberty (Tan ner genital stages IC and II) embody a physiologically unique sexual develo pmental window, marked by transiently enhanced LH and testosterone feedback stability in boys. Whether analogous plasticity of hypothalamo-pituitary-g onadal interactions unfolds during female adolescence is not known.