Orexin A suppresses in vivo GH secretion

Abstract

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 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 mg, i.c.v.) or vehicle (10 ml, 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 mg/kg, i.v.) although it markedly blunted GH responses to ghrelin (40 mg/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

Distribution of Orexin/Hypocretin Immunoreactivity in the Brain of the Lungfishes <i>Protopterus dolloi</i> and <i>Neoceratodus forsteri</i>

“…This strongly suggested that orexins might be involved in diverse functions and in subsequent studies they have been demonstrated to participate in the control of feeding and energy homeostasis [Lubkin and Stricker-Krongrad, 1998;Sakurai et al, 1998;Wolf, 1998;Dube et al, 1999;Haynes et al, 1999;Sweet et al, 1999;Volkoff et al, 1999Volkoff et al, , 2005Yamanaka et al, 1999;Karteris et al, 2005;Volkoff, 2006;Carter et al, 2009] or the regulation of the sleep-wake cycle and related pathologies such as narcolepsy [Chemelli et al, 1999;Hagan et al, 1999;Lin et al, 1999;Beuckmann and Kukkonen et al, 2002;Baumann and Bassetti, 2005;Matsuki and Sakurai, 2008;Takahashi et al, 2008]. In addition, orexins also regulate the release of adenohypophyseal hormones [Pu et al, 1998;Malendowicz et al, 1999;Mitsuma et al, 1999;Tamura et al, 1999;Russell et al, 2000;Kohsaka et al, 2001;Seoane et al, 2004;Barb and Matteri, 2005;Martynska et al, 2006], the integrated control of autonomic function [Shirasaka et al, 2002;Ferguson and Samson, 2003;Berthoud et al, 2005;Yasuda et al, 2005] and the stimulation of gastrointestinal functions [Okumura and Takakusaki, 2008]. In particular, regulation of food intake orexins has been demonstrated in teleost fishes [Volkoff et al, 1999;…”

Orexin-Induced Apoptosis: The Key Role of the Seven-Transmembrane Domain Orexin Type 2 Receptor

“…Orexins alter endocrine function (14) by increasing glucagon secretion and decreasing glucose-stimulated insulin release from pancreatic islets (15), suppressing GH secretion (16), or regulating corticotropin release (14).…”

Organization of the Orexin/Hypocretin System in the Brain of Holostean Fishes: Assessment of Possible Relationships with Monoamines and Neuropeptide Y

“…Previous studies have already dealt with the involvement of the orexinergic system in the control of the adenohypophysis [Kukkonen et al, 2002;Ferguson and Samson, 2003], regulating the liberation of ACTH, GH, gonadotropins, LH, and prolactin in rats [Pu et al, 1998;Kuru et al, 2000;Blanco et al, 2001;Kohsaka et al, 2001;Porkka-Heiskanen et al, 2004;Seoane et al, 2004;Kiyokawa et al, 2011;Cataldi et al, 2014]. Of note, orexins inhibit the gonadotropin-releasing hormone system that produces reproductive behavior in goldfish [Hoskins et al, 2008].…”