Glia-to-neuron Signaling and the Neuroendocrine Control of Female Puberty

The sine qua non event of puberty is an increase in pulsatile release of gonadotrophin hormone releasing hormone (GnRH). It is now clear that this increase and, therefore, the initiation of the pubertal process itself, require both changes in transsynaptic communication and the activation of glia-to-neuron signaling pathways. While neurons that utilize excitatory and inhibitory amino acids as transmitters represent major players in the transsynaptic control of puberty, glial cells utilize a combination of trophic factors and small cell-cell signaling molecules to regulate neuronal function and, thus, promote sexual development. A coordinated increase in glutamatergic transmission accompanied by a decrease in inhibitory GABAergic tone appears to initiate the transsynaptic cascade of events leading to the pubertal increase in GnRH release. Glial cells facilitate GnRH secretion via cell-cell signaling loops mainly initiated by members of the EGF and TGF- families of trophic factors, and brought about by either these factors themselves or by chemical messengers released in response to growth factor stimulation. In turn, a neuron-to-glia communication pathway mediated by excitatory amino acids serves to coordinate the simultaneous activation of transsynaptic and glia-to-neuron communication required for the advent of sexual maturity. A different--and perhaps higher--level of control may involve the transcriptional regulation of subordinate genes that, by contributing to neuroendocrine maturation, are required for the initiation of the pubertal process.