Neuroendocrine-immune (NEI) circuitry from neuron-glial interactions to function: Focus on gender and HPA-HPG interactions on early programming of the NEI system

Bidirectional communication between the neuroendocrine and immune systems d uring ontogeny plays a pivotal role in programming the development of neuro endocrine and immune responses in adult life. Signals generated by the hypo thalamic-pituitary-gonadal axis (i.e. luteinizing hormone-releasing hormone , LHRH, and sex steroids), and by the hypothalamic-pituitary-adrenocortical axis (glucocorticoids (GC)), are major players coordinating the developmen t of immune system function. Conversely, products generated by immune syste m activation exert a powerful and long-lasting regulation on neuroendocrine axes activity. The neuroendocrine-immune system is very sensitive to prepe rinatal experiences, including hormonal manipulations and immune challenges , which may influence the future predisposition to several disease entities . We review our work on the ongoing mutual regulation of neuroendocrine and immune cell activities, both at a cellular and molecular level. In the cen tral nervous system, one chief compartment is represented by the astroglial cell and its mediators. Hence, neuron-glial signalling cascades dictate ma jor changes in response to hormonal manipulations and pro-inflammatory trig gers. The interplay between LHRH, sex steroids, GC and pro-inflammatory med iators in some physiological and pathological states, together with the pot ential clinical implications of these findings, are summarized. The overall study highlights the plasticity of this intersystem cross-talk for pharmac ological targeting with drugs acting at the neuroendocrine-immune interface .