Orexins and the regulation of the hypothalamic-pituitary-testicular axis

Orexins (OX), OX-A and OX-B, were initially identified as hypothalamic neuropeptides primarily involved in the control of food intake and states of arousal. Thereafter, orexins have been substantiated as putative pleiotropic regulators of a wide diversity of biological systems, including different neuroendocrine axes. Among the latter, compelling experimental evidence has recently been documented that orexins, mainly OX-A, may act at different levels of the hypothalamic-pituitary-gonadal (HPG) axis to modulate reproductive function. These actions are likely to include regulatory effects on the hypothalamic centres governing the HPG axis, as well as direct actions at the gonadal level. We review herein the experimental evidence, gathered in recent years, supporting a reproductive 'facet' of orexins, with special emphasis on our current knowledge of their patterns of expression and potential functional roles in the testis. Overall, the available data strongly suggest that, by acting at different levels of the HPG axis, orexins may operate as putative neuroendocrine and autocrine/paracrine regulators of gonadal function.