The hypothalamic GnRH pulse generator: multiple regulatory mechanisms

Pulsatile secretion of gonadotropin-releasing hormone (GnRH) release is an intrinsic property of hypothalamic GnRH neurons. Pulse generation has been attributed to multiple specific mechanisms, including spontaneous electrical activity of GnRH neurons, calcium and cAMP signaling, a GnRH receptor autocrine regulatory component, a GnRH concentration-dependent switch in GnRH receptor (GnRH-R) coupling to specific G proteins, the expression of G protein-coupled receptors (GPCRs) and steroid receptors, and homologous and heterologous interactions between cell membrane receptors expressed in GnRH neurons. The coexistence of multiple regulatory mechanisms for pulsatile GnRH secretion provides a high degree of redundancy in maintaining this crucial component of the mammalian reproductive process. These studies provide insights into the basic cellular and molecular mechanisms involved in GnRH neuronal function.