Cellular Localization of Orexin Receptors in Human Pituitary*

Blanco, Montserrat; López, Miguel; García‐Caballero, Tomás; Gallego, Rosalı́a; Vázquez-Boquete, Ángel; Morel, Guillaume; Señarı́s, Rosa; Casanueva, Felipe F.; Diéguez, Carlos; Beiras, A.

doi:10.1210/jcem.86.7.7433

Cited by 39 publications

(24 citation statements)

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“…In addition to the effect of the hypocretins at the hypothalamic level, neuroanatomical studies support a direct effect on the anterior pituitary because both hypocretinergic receptors have been detected in this region (Blanco et al, 2001(Blanco et al, , 2003. The hypocretins have an inhibitory effect on CRF-stimulated ACTH release from anterior pituitary cells in vitro (Samson and Taylor, 2001).…”

Section: Discussionmentioning

confidence: 99%

Interaction between the Corticotropin-Releasing Factor System and Hypocretins (Orexins): A Novel Circuit Mediating Stress Response

Winsky‐Sommerer¹,

Yamanaka²,

Diano³

et al. 2004

J. Neurosci.

411

316

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The hypothalamic neuropeptides hypocretins (orexins) play a crucial role in the stability of arousal and alertness. We tested whether the hypocretinergic system is a critical component of the stress response activated by the corticotropin-releasing factor (CRF). Our results show that CRF-immunoreactive terminals make direct contact with hypocretin-expressing neurons in the lateral hypothalamus and that numerous hypocretinergic neurons express the CRF-R1/2 receptors. We also demonstrate that application of CRF to hypothalamic slices containing identified hypocretin neurons depolarizes membrane potential and increases firing rate in a subpopulation of hypocretinergic cells. CRF-induced depolarization was tetrodotoxin insensitive and was blocked by the peptidergic CRF-R1 antagonist astressin. Moreover, activation of hypocretinergic neurons in response to acute stress was severely impaired in CRF-R1 knock-out mice. Together, our data provide evidence of a direct neuroanatomical and physiological input from CRF peptidergic system onto hypocretin neurons. We propose that, after stressor stimuli, CRF stimulates the release of hypocretins and that this circuit contributes to activation and maintenance of arousal associated with the stress response.

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Section: Discussionmentioning

confidence: 99%

Interaction between the Corticotropin-Releasing Factor System and Hypocretins (Orexins): A Novel Circuit Mediating Stress Response

Winsky‐Sommerer¹,

Yamanaka²,

Diano³

et al. 2004

J. Neurosci.

411

316

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“…The OX-containing neurons project to multiple sites of the central nervous system (7,8). These peptides bind and activate two closely related G-protein coupled receptors, called OX receptor 1 (OX1R) and OX receptor 2 (OX2R), which are expressed in different parts of the central nervous system, as well as in certain peripheral tissues (3,(9)(10)(11). This wide distribution of OX fibres and OX receptors indicates that OXs may play an important role in physiological functions other than feeding.…”

Section: Introductionmentioning

confidence: 99%

Orexin A suppresses in vivo GH secretion

Seoane

Tovar

Pérez

et al. 2004

European Journal of Endocrinology

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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

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“…The above results suggest that the animals' hormonal milieu affects the orexin system. The expression of orexins and their receptors in the pituitary of humans (Blanco et al, 2001 and, rats (Date et al, 2000;Jöhren et al, 2003;Silveyra et al, 2007b) and pigs (receptors only) (Kaminski et al, 2010a) also supports the possibility that orexin participates in autocrine and/or paracrine control of the pituitary gland. OXA was found in lactotrophs, thyreotrophs, somatotrophs and gonadotrophs but not in corticotrophs in the human anterior pituitary.…”

Section: Introductionmentioning

confidence: 63%

“…In humans, OX1R was also more abundant in AP than in NP, and in the human AP, the cells immunostained for OX1R were much more numerous than the cells expressing OX2R protein. In the human AP, OX1R protein was expressed by somatotrophs and OX2R by corticotrophs (Blanco et al, 2001). In pigs, OX1R protein levels were higher in AP than in NP on days 10 to 12 of the cycle and OX2R protein expression was higher in AP thorough the entire cycle (Kaminski et al, 2010a).…”

mentioning

confidence: 93%

“…The above results indicate that NP is the main source of orexins in rats, whereas human lactotrophs are the main source of OXA and corticotrophs are the main source of OXB. The presence of OX1R and OX2R was demonstrated in rat (Date et al, 2000;Jöhren et al, 2001Jöhren et al, , 2003, human (Blanco et al, 2001), sheep (Zhang et al, 2005 and porcine pituitaries (Kaminski et al, 2010a). In rats, OX1R and OX2R genes were found in AP and NP.…”

mentioning

confidence: 97%

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The effect of the estrous cycle on the expression of prepro-orexin gene and protein and the levels of orexin A and B in the porcine pituitary

Smolińska

Nitkiewicz

Maleszka

et al. 2014

Animal

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Hypothalamic peptides orexin A (OXA) and orexin B (OXB) are derived from the proteolytic cleavage of a common precursor molecule, prepro-orexin (PPO). They act via two orexin receptors (OX1R and OX2R), which belong to the G-protein coupled receptor superfamily. Orexins are implicated in the regulation of arousal states, energy homeostasis and reproductive neuroendocrine function. The objective of this study was to investigate the presence and changes in orexin expression in the porcine pituitary during the estrous cycle. Adenohypophysis (AP) and neurohypophysis (NP) tissue samples were harvested on days 2 to 3, 10 to 12, 14 to 16, and 17 to 19 of the estrous cycle. The expression of the PPO gene increased in AP and NP during the estrous cycle. The highest PPO protein concentrations in AP were reported on days 2 to 3 (P < 0.05), and in NP -on days 10 to 12 and 17 to 19 ( P < 0.05). The expression of PPO mRNA was lower in AP than in NP, but PPO protein levels were higher in AP. In AP, OXA immunoreactivity was higher ( P < 0.05) on days 10 to 12 and 14 to 16. In NP, the highest ( P < 0.05) content of the analyzed protein was observed on days 10 to 12 and the lowest ( P < 0.05) -on days 14 to 16 and 17 to 19. OXB immunoreactivity in AP reached the highest level ( P < 0.05) on days 2 to 3, and the lowest level ( P < 0.05) was determined on days 10 to 12 and 17 to 19. OXB protein concentrations in NP peaked ( P < 0.05) on days 10 to 12 of the cycle. Our study was the first experiment to demonstrate the expression of the orexin gene and orexin proteins in the porcine pituitary and the correlations between expression levels and the phase of the estrous cycle. Keywords: prepro-orexin, orexin A and B, pituitary, estrous cycle, pig ImplicationsThe relationship between nutritional status and reproductive success in animals has been studied for many years. Considerable evidence has been accumulated to implicate the existence of a common endocrine system that controls metabolism and the reproductive system. It is suggested that orexins belong to the group of hormones, which regulate metabolic status and reproduction. In this study, we demonstrated differences in orexin gene and orexin proteins in the porcine pituitary during the estrous cycle. The results imply the impact of hormonal milieu on orexins' expression in the porcine pituitary. A sound knowledge of mechanisms that control energy homeostasis and reproduction is needed in animal breeding practice. IntroductionOrexin A and B (OXA, OXB), also known as hypocretin 1 and 2, are hypothalamic peptides with a 46% sequence homology. OXA is a 33-amino acid peptide with a molecular mass of~3.5 kDa, which has an N-terminal pyroglutamyl residue and C-terminal amidation. OXB is a 28-amino acid peptide with a molecular mass of~2.9 kDa and C-terminal amidation. Orexins are cleaved from a 130-amino acid common precursor molecule, prepro-orexin (PPO), which is synthesized mainly in neurons inside and in the area of the lateral and posterior hypothalamus. Orexin action is mediated ...

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Cellular Localization of Orexin Receptors in Human Pituitary*

Cited by 39 publications

References 0 publications

Interaction between the Corticotropin-Releasing Factor System and Hypocretins (Orexins): A Novel Circuit Mediating Stress Response

Interaction between the Corticotropin-Releasing Factor System and Hypocretins (Orexins): A Novel Circuit Mediating Stress Response

Orexin A suppresses in vivo GH secretion

The effect of the estrous cycle on the expression of prepro-orexin gene and protein and the levels of orexin A and B in the porcine pituitary

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