Figure 4. Multiple levels of GnRH neurosecretory control of the onset of puberty. In purple, the three central hierarchical levels of GnRH secretion control: 1° upstream controlling genes; 2° Kisspeptin system; 3° functional integration of neuronal and glial network. Upstream controlling genes (Oct2, TTF1, EAP1 et others) are transcriptional regulator of subordinate genes required for cell function and cell-cell communication of neurons and glial cells which compose a functional network. Kisspeptin system directs this network and also connects it to the peripheral systems (gonads and nutritional status). Positive and negative effects on GnRH secretion are indicated in red and blue, respectively.