Orexin A suppresses in vivo GH secretion.
OBJECTIVE
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 neuroendocrine 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 in vitro GH secretion.


METHODS
We administered OX-A (10 microg, i.c.v.) or vehicle (10 microl, 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+/-1.7 ng/ml vs 9.4+/-2.2 ng/ml; P<0.05), mean GH amplitude (3.6+/-0.5 ng/ml vs 20.8+/-5.6 ng/ml; P<0.01) and area under the curve (848+/-379 ng/ml per 4 h vs 1957+/-458 ng/ml per 4 h; P<0.05). In contrast, OX-A failed to modify in vivo GH responses to GHRH (10 microg/kg, i.v.) although it markedly blunted GH responses to ghrelin (40 microg/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 in 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.
Seoane
L M
LM
Department of Physiology, Endocrine Area Complejo Hospitalario Universitario de Santiago, University of Santiago, Santiago de Compostela, Spain.
Tovar
S A
SA
Perez
D
D
Mallo
F
F
Lopez
M
M
Señaris
R
R
Casanueva
F F
FF
Dieguez
C
C
D000204:Activity Cycles; D000818:Animals; D019540:Area Under Curve; D002352:Carrier Proteins / Q000494:pharmacology*; D054439:Ghrelin; D013006:Growth Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D000068797:Orexins; D036361:Peptide Hormones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002352:Carrier Proteins; D054439:Ghrelin; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D036361:Peptide Hormones; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone