Abstract
Orexins A and B are hypothalamic peptides derived from a precursor called prepro-orexin and are associated with the stimulation of food intake and arousal. There is evidence that orexins act on some pituitary functions. Since no studies have been done concerning the presence of orexins in human pituitary, it is unclear whether the local effect of these peptides is due to orexins synthesized in the pituitary or to circulating-derived orexins. To define a possible paracrine regulatory role of orexins on pituitary cell function, we have sought to characterize the expression of orexins in the human adenohypophysis as well as to identify the cell types that express these proteins. In the present study, we used immunohistochemistry and double labeling to detect the presence of orexin A and orexin B in human pituitary. Orexin A was localized in 33% of pituitary cells. With double immunofluorescence techniques we demonstrated that orexin A is present in PRL (82±5.3%), TSH (18±2.3%), GH (10±2.3%), FSH (8±2.6%), and LH (7±3.2%) cells, but not in corticotroph cells. Orexin B was found in virtually all corticotrophs cells of the anterior pituitary. These results demonstrate that lactotroph cells are the main source of orexin A and corticotroph cells of orexin B. In summary the present findings provide the first evidence that orexins A and B are expressed in specific human pituitary cell types. Our data provide the cellular basis for a paracrine role of orexins in human pituitary cell function and further our understanding regarding the mechanisms by which orexins influence neuroendocrine function.
Similar content being viewed by others
References
Blanco M, López M, García-Caballero T, Gallego R, Vázquez-Boquete A, Morel G, Señarís R, Casanueva F, Diéguez C, Beiras A (2001) Cellular localization of orexin receptors in human pituitary. J Clin Endocrinol Metab 86:1616–1619
Blanco M, García-Caballero T, Fraga M, Gallego R, Cuevas J, Forteza J, Beiras A, Diéguez C (2002) Cellular localization of orexin receptors in human adrenal gland, adrenocortical adenomas and pheochromocytomas. Regul Peptides 14:161–165
Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, Richardson JA, Williams SC, Xiong Y, Hisanuki Y, Fitch TE, Nakazato M, Hammer RE, Saper CB, Yanagisawa M (1999) Narcolepsy in orexin knockout mice: molecular genetics of sleep disorder narcolepsy. Cell 98:437–451
Date Y, Ueta Y, Yamashita H, Yamaguchi H, Matsukura S, Kangawa K, Sakurai T, Yanagisawa M, Nakazato M (1999) Orexins, orexigenic hypothalamic peptides, interact with autonomic, neuroendocrine and neuroregulatory systems. Proc Natl Acad Sci U S A 96:748–753
Date Y, Mondal MS, Matsukura S, Ueta Y, Yamashita H, Kaiya H, Kangawa K, Nakazato M (2000) Distribution of orexin/hypocretin in the rat median eminence and pituitary. Brain Res Mol Brain Res 76:1–6
de Lecea L, Kilduff TS, Peyron C, Gao X-B, Foye PE, Danielson PE, Fukuhara C, Battenberg ELF, Gautvik VT, Bartlett II FS, Frankel WN, van den Pol AN, Bloom FE, Gautvik KM, Sutcliffe JG (1998) The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci U S A 95:322–327
Kirchgessner AL, Liu MT (1999) Orexins synthesis and response in the gut. Neuron 24:941–951
Kok SW, Roelfsema F, Overeem S, Lammers GJ, Strijers RL, Frolich M, Meinders AE, Pijl H (2002) Dynamics of the pituitary-adrenal ensemble in hypocretin-deficient narcoleptic humans: blunted basal adrenocorticotropin release and evidence for normal time-keeping by the master pacemarker. J Clin Endocrinol Metab 87:5085–5091
Kuru M, Ueta Y, Serino R, Nakazato M, Yamamoto Y, Shibuya Y, Yamashita H (2000) Centrally administered orexin/hypocretin activates HPA axis in rats. Neuroendocrinology 2:1977–1980
López M, Señarís R, Gallego R, García-Caballero T, Lago F, Seoane L, Casanueva F, Diéguez C (1999) Orexin receptors are expressed in the adrenal medulla of the rat. Endocrinology 140:5991–5994
Mikkelsen JD, Hauser F, de Lecea L, Sutcliffe JG, Kilduff TS, Calgary C, Pévet P, Simonneaux V (2001) Hypocretin (orexin) in the rat pineal gland: a central transmitter with effects on noradrenaline-induced release of melatonin. Eur J Neurosci 14:419–425
Overeem S, Kok SW, Lammers GJ, Vein AA, Frolich M, Meinders AE, Roelfsema F, Pijl H (2002) Somatotropic axis in hypocretin-deficient narcoleptic humans: altered circadian distribution of GH secretory events. Am J Physiol Endocrinol Metab 284:E641–E647
Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG, Kilduff TS (1998) Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 18:9996–10015
Pu S, Jain MR, Kalra PS, Kalra SP (1998) Orexins, a novel family of hypothalamic neuropeptides, modulate pituitary luteinizing hormone secretion in an ovarian steroid-dependent manner. Regul Peptides 78:133–136
Russell SH, Kim MS, Small CJ, Abbott CR, Morgan DG, Taheri S, Murphy KG, Todd JF, Ghatei MA; Bloom SR (2000) Central administration of orexin A suppresses basal and domperidone stimulated plasma prolactin. J Neuroendocrinol 12:1213–1218
Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Wiliams SC, Richardson JA, Kozlowski GP, Wilson S, Arch JRS, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu W-S, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M (1998) Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behaviour. Cell 92:573–585
Samson WK, Gosnell B, Chang JK, Resch ZT, Murphy TC (1999) Cardiovascular regulatory actions of the hypocretins in brain. Brain Res 831:248–253
Sánchez de Miguel MJ, Burrel MA (2002) Immunocytochemical detection of orexin A in endocrine cells of the developing mouse gut. J Histochem Cytochem 50:63–69
Shirasaka T, Nakazato M, Matsukura S, Takasaki M, Kannan H (1999) Sympathetic and cardiovascular actions of orexins in conscious rats. Am J Physiol 277:R1780–R1785
Trivedi P, Yu H, MacNeil DJ, van der Ploeg LHT, Guan X-M (1998) Distribution of orexin receptor mRNA in the rat brain. FEBS Lett 438:71–75
Xu R, Wang Q, Yan M, Hernández M, Gong C, Boon WC, Murata Y, Ueta Y, Chen C (2002) Orexin-A augments voltage-gated Ca2+ currents and synergistically increases growth hormone (GH) secretion with GH-releasing hormone in primary cultured ovine somatotropes. Endocrinology 143:4609–4619
Xu R, Roh SG, Gong C, Hernández M, Ueta Y, Chen C (2003) Orexin-B augments voltage-gated L-type Ca(2+) current via protein kinase C-mediated signalling pathway in ovine somatotropes. Neuroendocrinology 77:141–152
Acknowledgements
We thank the expert technical assistance of D. Fernández-Roel. This study was supported by the Xunta de Galicia (grant number PGIDIT02PXIB2080PR). M.B. is a recipient of a studentship from the Xunta de Galicia
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Blanco, M., Gallego, R., García-Caballero, T. et al. Cellular localization of orexins in human anterior pituitary. Histochem Cell Biol 120, 259–264 (2003). https://doi.org/10.1007/s00418-003-0562-z
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00418-003-0562-z