Orexins are a newly described family of hypothalamic neuropeptides. Based on the distribution of orexin neurons and their receptors in the brain, it has been postulated that they could play a role in the regulation of neuroendocrine function. Growth hormone (GH) secretion is markedly influenced by nutritional status and body weight. To investigate the role orexin A plays in the neuroregulation of GH secretion we have studied its effect on spontaneous GH secretion as well as GH responses to GHRH and ghrelin in freely moving rats. Finally, we also assessed the effect of orexin A on in vitro GH secretion.

Chronic intracerebroventricular and intravenous cannulae were implanted under ketamine-xylazine anaesthesia. We administered orexin A (10 µg, I.C.V.) or vehicle (10 µl, I.C.V.) to freely moving rats. Spontaneous GH secretion was assessed for 6 h with blood samples taken every 15 min. The animals were humanely killed. Administration of orexin A led to a decrease in spontaneous GH secretion in comparison with vehicle-treated rats, as assessed by mean GH levels (4.2 ± 1.7 vs. 9.4 ± 2.2 ng ml^-1; P < 0.05), mean GH amplitude (3.6 ± 0.5 vs. 20.8 ± 5.6 ng ml^-1; P < 0.01) and area under the curve (848 ± 379 vs. 1957 ± 458 ng ml^-1 (4 h)^-1; P < 0.05). In contrast, orexin A failed to modify in vivo GH responses to GHRH (10 µg kg^-1; I.V.) although it markedly blunted GH responses to ghrelin (40 µg kg^-1; I.V.) (mean peak GH levels: 331 ± 71 ng ml^-1, vehicle, vs. 43 ± 11 ng ml^-1 in orexin A-treated rats: P < 0.01). Data are expressed as means ± S.E.M. Comparison between the different groups was assessed by the Mann-Whitney test. These data indicate that orexin A plays an inhibitory role on GH secretion and may act as a bridge among the regulatory signals that are involved in the control of growth and nutritional status.

This work was supported by Fondo de Investigaciones Sanitarias, Spanish Ministry of Health, Spanish Ministry of Education, DGICYT, and European Union.