Much has been learned in recent years about the neuroendocrine mechanisms controlling the initiation of female reproductive function. It requires changes in the release of gonadotropin-releasing hormone (GnRH) from neurosecretory neurons mostly located in the medial basal hypothalamus of primates, and the preoptic region of rodents 1, 2. These changes are, in turn, determined by modifications in transsynaptic 3 and glial 4 inputs to the GnRH neuronal network. While the transsynaptic changes involve an increase in excitatory inputs and a reduction in inhibitory influences 1, the glial component is predominantly facilitatory, and exerted by both growth factors and small molecules that directly or indirectly stimulate GnRH secretion 4. The direct excitatory transsynaptic regulation of GnRH secretion is provided by at least three different neuronal subsets: kisspeptin neurons acting via GPR54 receptors 5, glutamatergic neurons acting mostly via AMPA receptors 6, 7, but also NMDA receptors 7, 8, and GABA acting via ionotropic GABAA receptors 9. The inhibitory counterpart of this circuitry depends principally on GABAergic neurons acting via GABAB metabotropic receptors 9, but also on opiatergic neurons that employ different peptides and a variety of different receptors for inhibitory neurotransmission [reviewed in 1].
