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dc.contributor.authorLuque, R.M.
dc.contributor.authorCórdoba-Chacón, J.
dc.contributor.authorGesmundo, I.
dc.date.accessioned2016-01-13T20:15:02Z
dc.date.available2017-01-14T10:30:05Z
dc.date.issued2014-04
dc.identifier.bibliographicCitationLuque, R. M., Cordoba-Chacon, J., Ibanez-Costa, A., Gesmundo, I., Grande, C., Gracia-Navarro, F., Tena-Sempere, M., Ghigo, E., Gahete, M. D., Granata, R., Kineman, R. D. and Castano, J. P. Obestatin Plays an Opposite Role in the Regulation of Pituitary Somatotrope and Corticotrope Function in Female Primates and Male/Female Mice. Endocrinology. 2014. 155(4): 1407-1417. 10.1210/en.2013-1728.en_US
dc.identifier.issn: 0013-7227
dc.identifier.urihttp://hdl.handle.net/10027/19960
dc.descriptionThis is a copy of an article published in Endocrinology © 2014 Endocrine Society Publications. endo.endojournals.orgen_US
dc.description.abstractObestatin is a 23-amino-acid amidated peptide that is encoded by the ghrelin gene. Previous studies have shown obestatin can modulate the hypothalamic neuronal circuitry that regulates pituitary function, perhaps by modulating the actions of ghrelin. However, the direct actions of obestatin on pituitary function remain controversial. Here, primary pituitary cell cultures from a nonhuman primate (baboon) and mice were used to test the effects of obestatin on pituitary hormone expression and secretion. In pituitary cultures from both species, obestatin had no effect on prolactin, LH, FSH, or TSH expression/release. Conversely, obestatin stimulated proopiomelanocortin expression and ACTH release and inhibited GH expression/release in vitro, actions that were also observed in vivo in mice treated with obestatin. In vitro, obestatin inhibited the stimulatory actions of ghrelin on GH but not ACTH release. The inhibitory effect of obestatin on somatotrope function was associated with an overall reduction in pituitary transcription factor-1 and GHRH receptor mRNA levels in vitro and in vivo as well as a reduction in hypothalamic GHRH and ghrelin expression in vivo. The stimulatory effect of obestatin on ACTH was associated with an increase in pituitary CRF receptors. Obestatin also reduced the expression of pituitary somatostatin receptors (sst1/sst2), which could serve to modify its impact on hormone secretion. The in vitro actions of obestatin on both GH and ACTH release required the adenylyl cyclase and MAPK routes. Taken together, our results provide evidence that obestatin can act directly at the pituitary to control somatotrope and corticotrope function, and these effects are conserved across speciesen_US
dc.description.sponsorshipThis work was supported by the following grants: Junta de Andalucía (BIO-0139, CTS-5051, CTS-1406, PI-0369 –2012), Ministerio de Economía y Competitividad, Gobierno de España (BFU2010 –19300), Instituto de Salud Carlos III (PI13/00651, and “Sara Borell Program” CD11/00276), Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBERobn) and Ayuda Merck Serono 2013 (to R.M.L, A.I.-C., M.D.G., and J.P.C) and BFI2011-25021 (to M.T.-S.); Compagnia di San Paolo 2011 and Ministero dell’Istruzione, dell’Università e della Ricerca 2009 (to R.G.); Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development Merit Award and the National Institutes of Health Grants R21AG031465 and R01DK088133 (to R.D.K.). Ciber is an initiative of Instituto de Salud Carlos III, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain.en_US
dc.publisherEndocrine Societyen_US
dc.subjectNoneen_US
dc.titleObestatin Plays an Opposite Role in the Regulation of Pituitary Somatotrope and Corticotrope Function in Female Primates and Male/Female Miceen_US
dc.typeArticleen_US


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