Sex-specific association between urinary kisspeptin and pubertal development

Kisspeptins are critical neuropeptides for puberty onset and progression, playing a pivotal role in the reactivation of the hypothalamus-pituitary-gonadal axis in late childhood. Despite their importance, little is known as to how kisspeptin peripheral concentrations are related to sexual maturation in humans, specially using non-invasive measures that allow more widespread testing. Using a cross-sectional design, we investigated whether peripheral kisspeptin concentrations, measured by enzyme-linked immunosorbent assays (ELISA) in two-hour retention midstream urine, are associated with developmental markers in 209 (120 girls) typically developing, 9 to 15-year-olds. Developmental variables were age, self-reported pubertal status using the Pubertal Development Scale, and saliva concentrations of hormones that indicate gonadal (testosterone) and adrenal (dehydroepiandrosterone sulfate) functioning. We found marked sexual differences in urine kisspeptins (controlled for body mass index and socioeconomic status). While concentrations were similar in both sexes until the age of around 12 years, in males there was a positive linear correlation with all developmental measures thereafter, while in girls, kisspeptin concentrations did not change. Of note, our results are in line with those of previous studies using more invasive methods (e.g. blood samples), which indicates that kisspeptin concentrations from two-hour retention midstream urine have potential in exploring sex-specific peripheral action of these peptides.