Immunological influences on reproductive neuroendocrinology

One of the consequences of activation of the immune system, with its associated inflammatory responses and operation of the stress axes, is a generalised inhibition of reproductive function. This can be considered as part of the all-encompassing effects of an activated immune system, included in which is the 'immunological cost' arising from the nutritional demand required to maintain a competent, responsive immune system, and the pathological effects produced by severe immune responses. Elucidation of specific immune-neuroendocrine linkages has largely involved examination of corticosteroid-based mechanisms or use of bacterial endotoxin as a model stimulus and examination of effects on GnRH and LH pulsatility, on GnRH and LH surge processes and on pituitary responsiveness to GnRH, using various sheep models. Although there is good evidence for prostaglandins as common mediators for endotoxin-induced and stress axis-induced impairment of neuroendocrine reproductive processes, both mechanisms appear to have prostaglandin-independent pathways as well. At the anterior pituitary gland level, the type II glucocorticoid receptor appears to mediate corticosteroid effects. Otherwise, the identity of specific cytokines, their sites of action and the cell level mechanisms underlying the inhibition of the reproductive axis at hypothalamic and anterior pituitary levels, especially in sheep, remains largely unresolved.