Physiology of Gonadotropin-Releasing Hormone (GnRH) : Beyond the Control of Reproductive Functions

GnRH is the hypothalamic main regulator of the hypothalamic-pituitary-gonadal reproductive axis, but it was found to exert additional functions due to the wide distribution of its receptors both in central nervous system (from cortex to spinal cord) and in peripheral organs and tissues. The possible activity of GnRH/GnRHR system at the level of the hippocampus has raised the interest on the effects of the decapeptide and its analogues on neurogenesis and neuronal functions. Recently, it has been observed that GnRH is decreased in mouse hypothalamic ageing and that restoring normal GnRH levels may attenuate brain and systemic aging processes. Other studies have also pointed out on neurogenic and neuro protective actions of GnRH in several models of neurodegeneration, as in Alzheimer's disease and in spinal cord injury models. A direct effect of GnRH on cholesterol and estrogen synthesis in human neuronal-like cells has been also proposed as a mechanism involved in neuro protective activity. Since GnRH analogues are known to be safe and effective, a new possible lines of therapeutic intervention to control some of the defects present in aging and neurodegenerative diseases may be delineated. In conclusion, brain GnRH/GnRHR system is a novel and extremely interesting target, since it mediates several actions possibly integrated in a complex control of reproductive functions with neurogenesis, neuroprotection, sex behavior and cognition.