Orexin A suppresses in vivo GH secretion

Background/aims: Orexins (OXs) are a newly described family of hypothalamic neuropeptides. Based on the distribution of OX neurons and their receptors in the brain, it has been postulated that they could play a role in the regulation of neuroendocrinc function. GH secretion is markedly influenced by nutritional status and body weight. To investigate the role OX-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 OX-A on ill vitro GH secretion. Methods: We administered OX-A (10 mug, i.c.v) or vehicle (10 mud. i.c.v.) to freely moving rats. Spontaneous GH secretion was assessed over 6 h with blood samples taken every 15 min. Results: Administration of OX-A led to a decrease in spontaneous GH secretion in comparison with vehicle-treated rats, as assessed by mean GH levels (means +/- S.E.M. 4.2 +/- 1.7ng/ml vs 9.4 +/- 2.2 ng/ml: P < 0.05), mean GH amplitude (3.6 +/- 0.5ng/ml vs 20.8 +/- 5.6ng/ml; P < 0.01) and area under the curve (848 +/- 379 ng/ml per 4h vs 1957 +/- 458ng/ml per 4h: P < 0.05). In contrast. OX-A failed to modify ill vivo GH responses to GHRH (10 mug/kg. i.v.) although it markedly blunted GH responses to ghrelin (40 mug/kg, i.v.) (mean peak GH levels: 331 +/- 71 ng/ml, vehicle. vs 43 +/- 11 ng/ml in OX-A-treated rats: P < 0.01). Finally, OX-A infusion (10(-7), 10(-8) or 10(-9)M) failed to modify ill vitro basal GH secretion or GH responses to GHRH, ghrelin and KCl. Conclusions: These data indicate that OX-A plays an inhibitory role in GH secretion and may act as a bridge among the regulatory signals that are involved in the control of growth. nutritional status and sleep regulation.