It is well known that nutritional state can profoundly affect endocrine functions, and that the hypothalamus plays a key role in integrating the neuroendocrine system and ingestive behavior. Orexin-A and -B, which are novel orexigenic peptides discovered in 1998, are mainly synthesized in the lateral hypothalamic area, which is a feeding center in the brain. As orexin-immunopositive fibers are widely projected to various parts of the central nervous system, including the endocrine hypothalamus, it is not surprising that the literature to date indicates　some neuroendocrine actions of orexins.

In this review, we focus on the knowledge presently available on the interplay between orexins and the neuroendocrine system, including some of our own findings. With respect to the hypothalamo-pituitary-adrenal axis, published studies suggest that orexins may be basically stimulatory to this endocrine axis via the upregulation of the corticotropin-releasing hormone and arginine vasopressin secretion directly, and also involving neuropeptide Y indirectly. With regard to the reproductive system, it has been reported that orexins exert both stimulatory and inhibitory effects on luteinizing hormone secretion, depending on the presence or absence of ovarian steroids. Our own data indicate that orexin-A positively regulates the estrogen-induced prolactin surge. However, the underlying mechanisms mediating this action remain to be elucidated. Concerning the hypothalamo-pituitary-thyroid axis, the literature indicates an inhibitory action of orexin-A on thyrotropin secretion, whereas the neurohormone does not appear to affect thyroid hormone production. With respect to growth hormone, orexins exert an inhibitory effect on its secretion. Collectively, it appears that orexins play a significant role in regulating a variety of neuroendocrine functions, in addition to their originally demonstrated action on feeding behavior. Orexins may represent hormonally active orexigenic peptides linking nutrition and neuroendocrine functions.