The genetic basis for the timing of human puberty.

Puberty is a complex, coordinated biological process with multiple levels of regulation. Epidemiological observations suggest that the timing of pubertal events is a heritable trait, although environmental factors can modulate such genetic influence. The study of pathological states of early and late puberty has provided valuable insight into those genes that regulate gonadotrophin-releasing hormone (GnRH) activity. The development of pulsatile release of GnRH secretion mediated through kisspeptin-1 activation of G-protein coupled receptor-54 appears to be a central event at the onset and during progression of puberty. Stimulating and restraining influences (e.g. in the form of glutamatergic and GABAergic neuronal inputs) are likely to influence the timing of this process. The study of extreme variants of 'normality', such as constitutional delay of growth and puberty and early puberty, may lead to the recognition of additional genes and pathways that can modulate both the timing of pubertal onset and its tempo.