{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T10:10:58Z","timestamp":1780567858199,"version":"3.54.1"},"reference-count":37,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,4,1]]},"abstract":"<jats:p>Obestatin 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 species.<\/jats:p>","DOI":"10.1210\/en.2013-1728","type":"journal-article","created":{"date-parts":[[2014,1,31]],"date-time":"2014-01-31T16:38:12Z","timestamp":1391186292000},"page":"1407-1417","source":"Crossref","is-referenced-by-count":14,"title":["Obestatin Plays an Opposite Role in the Regulation of Pituitary Somatotrope and Corticotrope Function in Female Primates and Male\/Female Mice"],"prefix":"10.1210","volume":"155","author":[{"given":"Ra\u00fal M.","family":"Luque","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Physiology, and Immunology (R.M.L., J.C.-C., A.I.-C., F.G.-N., M.T.-S., M.D.G., J.P.C.), University of Cordoba, Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba, Hospital Universitario Reina Sofia, and Centros de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n, E-14014 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"C\u00f3rdoba-Chac\u00f3n","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Physiology, and Immunology (R.M.L., J.C.-C., A.I.-C., F.G.-N., M.T.-S., M.D.G., J.P.C.), University of Cordoba, Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba, Hospital Universitario Reina Sofia, and Centros de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n, E-14014 C\u00f3rdoba, Spain"},{"name":"Department of Medicine (J.C.-C., R.D.K.), Research and Development Division, Chicago, Illinois 60612"},{"name":"University of Illinois at Chicago, and Jesse Brown Veterans Affairs Medical Center (J.C.-C., R.D.K.), Research and Development Division, Chicago, Illinois 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Ib\u00e1\u00f1ez-Costa","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Physiology, and Immunology (R.M.L., J.C.-C., A.I.-C., F.G.-N., M.T.-S., M.D.G., J.P.C.), University of Cordoba, Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba, Hospital Universitario Reina Sofia, and Centros de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n, E-14014 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iacopo","family":"Gesmundo","sequence":"first","affiliation":[{"name":"Department of Medical Sciences (I.G., C.G., E.G., R.G.), University of Torino, 10126 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Grande","sequence":"first","affiliation":[{"name":"Department of Medical Sciences (I.G., C.G., E.G., R.G.), University of Torino, 10126 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Gracia-Navarro","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Physiology, and Immunology (R.M.L., J.C.-C., A.I.-C., F.G.-N., M.T.-S., M.D.G., J.P.C.), University of Cordoba, Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba, Hospital Universitario Reina Sofia, and Centros de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n, E-14014 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Tena-Sempere","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Physiology, and Immunology (R.M.L., J.C.-C., A.I.-C., F.G.-N., M.T.-S., M.D.G., J.P.C.), University of Cordoba, Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba, Hospital Universitario Reina Sofia, and Centros de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n, E-14014 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezio","family":"Ghigo","sequence":"first","affiliation":[{"name":"Department of Medical Sciences (I.G., C.G., E.G., R.G.), University of Torino, 10126 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel D.","family":"Gahete","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Physiology, and Immunology (R.M.L., J.C.-C., A.I.-C., F.G.-N., M.T.-S., M.D.G., J.P.C.), University of Cordoba, Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba, Hospital Universitario Reina Sofia, and Centros de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n, E-14014 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccarda","family":"Granata","sequence":"first","affiliation":[{"name":"Department of Medical Sciences (I.G., C.G., E.G., R.G.), University of Torino, 10126 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhonda D.","family":"Kineman","sequence":"first","affiliation":[{"name":"Department of Medicine (J.C.-C., R.D.K.), Research and Development Division, Chicago, Illinois 60612"},{"name":"University of Illinois at Chicago, and Jesse Brown Veterans Affairs Medical Center (J.C.-C., R.D.K.), Research and Development Division, Chicago, Illinois 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justo P.","family":"Casta\u00f1o","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Physiology, and Immunology (R.M.L., J.C.-C., A.I.-C., F.G.-N., M.T.-S., M.D.G., J.P.C.), University of Cordoba, Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba, Hospital Universitario Reina Sofia, and Centros de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n, E-14014 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"issue":"5750","key":"2020071612041019700_B1","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1126\/science.1117255","article-title":"Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake","volume":"310","author":"Zhang","year":"2005","journal-title":"Science"},{"issue":"9","key":"2020071612041019700_B2","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1369\/jhc.2008.951145","article-title":"Distribution of obestatin and ghrelin in human tissues: immunoreactive cells in the gastrointestinal tract, pancreas, and mammary glands","volume":"56","author":"Gr\u00f6nberg","year":"2008","journal-title":"J Histochem Cytochem"},{"issue":"4","key":"2020071612041019700_B3","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1210\/en.2006-1231","article-title":"Obestatin partially affects ghrelin stimulation of food intake and growth hormone secretion in rodents","volume":"148","author":"Zizzari","year":"2007","journal-title":"Endocrinology"},{"key":"2020071612041019700_B4","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1159\/000318512","article-title":"Ghrelin and anterior pituitary function","volume":"38","author":"Lanfranco","year":"2010","journal-title":"Front Horm Res"},{"issue":"4","key":"2020071612041019700_B5","doi-asserted-by":"crossref","first-page":"967","DOI":"10.2337\/db07-1104","article-title":"Obestatin promotes survival of pancreatic \u03b2-cells and human islets and induces expression of genes involved in the regulation of \u03b2-cell mass and function","volume":"57","author":"Granata","year":"2008","journal-title":"Diabetes"},{"issue":"5813","key":"2020071612041019700_B6","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1126\/science.1135047","article-title":"Comment on \u201cObestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake.\u201d","volume":"315","author":"Chartrel","year":"2007","journal-title":"Science"},{"issue":"2","key":"2020071612041019700_B7","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1210\/en.2006-1275","article-title":"Normal food intake and body weight in mice lacking the G protein-coupled receptor GPR39","volume":"148","author":"Tremblay","year":"2007","journal-title":"Endocrinology"},{"issue":"7","key":"2020071612041019700_B8","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1111\/j.1365-2826.2010.02019.x","article-title":"The ghrelin\/obestatin balance in the physiological and pathological control of growth hormone secretion, body composition and food intake","volume":"22","author":"Hassouna","year":"2010","journal-title":"J Neuroendocrinol"},{"issue":"3","key":"2020071612041019700_B9","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s12020-011-9453-6","article-title":"Biological effects of obestatin","volume":"39","author":"Li","year":"2011","journal-title":"Endocrine"},{"issue":"2\u20134","key":"2020071612041019700_B10","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1159\/000334106","article-title":"Obestatin: an interesting but controversial gut hormone","volume":"59","author":"Lacquaniti","year":"2011","journal-title":"Ann Nutr Metab"},{"issue":"4","key":"2020071612041019700_B11","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1016\/j.bbrc.2009.10.163","article-title":"Role of obestatin on growth hormone secretion: An in vitro approach","volume":"390","author":"Pazos","year":"2009","journal-title":"Biochem Biophys Res Commun"},{"issue":"8","key":"2020071612041019700_B12","doi-asserted-by":"crossref","first-page":"RC16","DOI":"10.1007\/BF03344175","article-title":"Obestatin inhibits feeding but does not modulate GH and corticosterone secretion in the rat","volume":"29","author":"Bresciani","year":"2006","journal-title":"J Endocrinol Invest"},{"issue":"2\u20133","key":"2020071612041019700_B13","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.regpep.2006.09.001","article-title":"Neither intravenous nor intracerebroventricular administration of obestatin affects the secretion of GH, PRL, TSH and ACTH in rats","volume":"138","author":"Yamamoto","year":"2007","journal-title":"Regul Pept"},{"issue":"1","key":"2020071612041019700_B14","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1210\/en.2006-0915","article-title":"Effects of obestatin on energy balance and growth hormone secretion in rodents","volume":"148","author":"Nogueiras","year":"2007","journal-title":"Endocrinology"},{"issue":"1","key":"2020071612041019700_B15","doi-asserted-by":"crossref","first-page":"R637","DOI":"10.1152\/ajpregu.00395.2006","article-title":"Obestatin acts in brain to inhibit thirst","volume":"292","author":"Samson","year":"2007","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"issue":"1","key":"2020071612041019700_B16","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/oby.2003.12","article-title":"The baboon as a nonhuman primate model for the study of the genetics of obesity","volume":"11","author":"Comuzzie","year":"2003","journal-title":"Obes Res"},{"key":"2020071612041019700_B17","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/B978-0-12-039228-5.50014-0","article-title":"Nonhuman primate models for human disease","volume":"28","author":"McClure","year":"1984","journal-title":"Adv Vet Sci Comp Med"},{"issue":"2","key":"2020071612041019700_B18","doi-asserted-by":"crossref","first-page":"E395","DOI":"10.1152\/ajpendo.00038.2006","article-title":"Evidence that endogenous SST inhibits ACTH and ghrelin expression by independent pathways","volume":"291","author":"Luque","year":"2006","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"9","key":"2020071612041019700_B19","doi-asserted-by":"crossref","first-page":"4440","DOI":"10.1210\/en.2007-0441","article-title":"Evidence that ghrelin is as potent as growth hormone (GH)-releasing hormone (GHRH) in releasing GH from primary pituitary cell cultures of a nonhuman primate (Papio anubis), acting through intracellular signaling pathways distinct from GHRH","volume":"148","author":"Kineman","year":"2007","journal-title":"Endocrinology"},{"issue":"1","key":"2020071612041019700_B20","doi-asserted-by":"crossref","first-page":"E46","DOI":"10.1152\/ajpendo.00514.2010","article-title":"Somatostatin and its receptors contribute in a tissue-specific manner to the sex-dependent metabolic (fed\/fasting) control of growth hormone axis in mice","volume":"300","author":"C\u00f3rdoba-Chac\u00f3n","year":"2011","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"3","key":"2020071612041019700_B21","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1210\/en.2010-1142","article-title":"Kisspeptin regulates gonadotroph and somatotroph function in nonhuman primate pituitary via common and distinct signaling mechanisms","volume":"152","author":"Luque","year":"2011","journal-title":"Endocrinology"},{"issue":"8","key":"2020071612041019700_B22","doi-asserted-by":"crossref","first-page":"3393","DOI":"10.1096\/fj.11-201343","article-title":"Obestatin regulates adipocyte function and protects against diet-induced insulin resistance and inflammation","volume":"26","author":"Granata","year":"2012","journal-title":"FASEB J"},{"issue":"12","key":"2020071612041019700_B23","doi-asserted-by":"crossref","first-page":"4800","DOI":"10.1210\/en.2011-1542","article-title":"Cortistatin is not a somatostatin analogue but stimulates prolactin release and inhibits GH and ACTH in a gender-dependent fashion: potential role of ghrelin","volume":"152","author":"C\u00f3rdoba-Chac\u00f3n","year":"2011","journal-title":"Endocrinology"},{"issue":"1","key":"2020071612041019700_B24","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1210\/en.2011-1677","article-title":"Homologous and heterologous in vitro regulation of pituitary receptors for somatostatin, growth hormone (GH)-releasing hormone, and ghrelin in a nonhuman primate (Papio anubis)","volume":"153","author":"C\u00f3rdoba-Chac\u00f3n","year":"2012","journal-title":"Endocrinology"},{"issue":"7","key":"2020071612041019700_B25","doi-asserted-by":"crossref","DOI":"10.1186\/gb-2002-3-7-research0034","article-title":"Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes","volume":"3","author":"Vandesompele","year":"2002","journal-title":"Genome Biol"},{"issue":"16","key":"2020071612041019700_B26","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1038\/onc.2011.389","article-title":"The new truncated somatostatin receptor variant sst5TMD4 is associated to poor prognosis in breast cancer and increases malignancy in MCF-7 cells","volume":"31","author":"Dur\u00e1n-Prado","year":"2012","journal-title":"Oncogene"},{"issue":"1\u20132","key":"2020071612041019700_B27","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.mce.2007.12.005","article-title":"Role of endogenous somatostatin in regulating GH output under basal conditions and in response to metabolic extremes","volume":"286","author":"Luque","year":"2008","journal-title":"Mol Cell Endocrinol"},{"key":"2020071612041019700_B28","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/j.1749-6632.2008.03660.x","article-title":"Understanding the multifactorial control of growth hormone release by somatotropes: lessons from comparative endocrinology","volume":"1163","author":"Gahete","year":"2009","journal-title":"Ann N Y Acad Sci"},{"issue":"5","key":"2020071612041019700_B29","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1111\/j.1460-9568.2011.07787.x","article-title":"Ghrelin and obestatin modulate growth hormone-releasing hormone release and synaptic inputs onto growth hormone-releasing hormone neurons","volume":"34","author":"Feng","year":"2011","journal-title":"Eur J Neurosci"},{"issue":"12","key":"2020071612041019700_B30","doi-asserted-by":"crossref","first-page":"5694","DOI":"10.1210\/endo.136.12.7588325","article-title":"In vitro characterization of four novel classes of growth hormone-releasing peptide","volume":"136","author":"Elias","year":"1995","journal-title":"Endocrinology"},{"issue":"1","key":"2020071612041019700_B31","first-page":"2","article-title":"POU domain factors in the neuroendocrine system: lessons from developmental biology provide insights into human disease","volume":"22","author":"Andersen","year":"2001","journal-title":"Endocr Rev"},{"issue":"6","key":"2020071612041019700_B32","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.1210\/en.2005-1549","article-title":"Impact of obesity on the growth hormone axis: evidence for a direct inhibitory effect of hyperinsulinemia on pituitary function","volume":"147","author":"Luque","year":"2006","journal-title":"Endocrinology"},{"issue":"1","key":"2020071612041019700_B33","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1677\/jme.1.02042","article-title":"Examination of the direct effects of metabolic factors on somatotrope function in a non-human primate model, Papio anubis","volume":"37","author":"Luque","year":"2006","journal-title":"J Mol Endocrinol"},{"issue":"7","key":"2020071612041019700_B34","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1210\/en.2013-1261","article-title":"Insulin and IGF-I inhibit GH synthesis and release in vitro and in vivo by separate mechanisms","volume":"154","author":"Gahete","year":"2013","journal-title":"Endocrinology"},{"key":"2020071612041019700_B35","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0083-6729(08)61069-9","article-title":"Control of ACTH secretion by corticotropin-releasing factor(s)","volume":"37","author":"Brodish","year":"1979","journal-title":"Vitam Horm"},{"issue":"4","key":"2020071612041019700_B36","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/path.2551","article-title":"Obestatin in human neuroendocrine tissues and tumours: expression and effect on tumour growth","volume":"218","author":"Volante","year":"2009","journal-title":"J Pathol"},{"issue":"9","key":"2020071612041019700_B37","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1111\/j.1582-4934.2010.01192.x","article-title":"Obestatin as a regulator of adipocyte metabolism and adipogenesis","volume":"15","author":"Gurriar\u00e1n-Rodr\u00edguez","year":"2011","journal-title":"J Cell Mol Med"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/155\/4\/1407\/10825417\/endo1407.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/155\/4\/1407\/10825417\/endo1407.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T20:52:24Z","timestamp":1716497544000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/155\/4\/1407\/2423311"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,4,1]]},"references-count":37,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,4,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2013-1728","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,4,1]]}}}