{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T14:53:12Z","timestamp":1772463192068,"version":"3.50.1"},"reference-count":62,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,11,1]]},"abstract":"<jats:p>Hexarelin (HEX) is a peptide GH secretagogue with a potent ability to stimulate GH secretion and recently reported cardioprotective actions. However, its effects in the brain are largely unknown, and the aim of the present study was to examine the potential protective effect of HEX on the central nervous system after injury, as well as on caspase-3, Akt, and extracellular signal-regulated protein kinase (ERK) signaling cascades in a rat model of neonatal hypoxia-ischemia. Hypoxic-ischemic insult was induced by unilateral carotid ligation and hypoxic exposure (7.7% oxygen), and HEX treatment was administered intracerebroventricularly, directly after the insult. Brain damage was quantified at four coronal levels and by regional neuropathological scoring. Brain damage was reduced by 39% in the treatment group, compared with vehicle group, and injury was significantly reduced in the cerebral cortex, hippocampus, and thalamus but not in the striatum. The cerebroprotective effect was accompanied by a significant reduction of caspase-3 activity and an increased phosphorylation of Akt and glycogen synthase kinase-3\u03b2, whereas ERK was unaffected. In conclusion, we demonstrate for the first time that HEX is neuroprotective in the neonatal setting in vivo and that increased Akt signaling is associated with downstream attenuation of glycogen synthase kinase-3\u03b2 activity and caspase-dependent cell death.<\/jats:p>","DOI":"10.1210\/en.2005-0389","type":"journal-article","created":{"date-parts":[[2005,8,5]],"date-time":"2005-08-05T00:34:31Z","timestamp":1123202071000},"page":"4665-4672","source":"Crossref","is-referenced-by-count":26,"title":["Growth Hormone-Releasing Peptide Hexarelin Reduces Neonatal Brain Injury and Alters Akt\/Glycogen Synthase Kinase-3\u03b2 Phosphorylation"],"prefix":"10.1210","volume":"146","author":[{"given":"Katarina G.","family":"Brywe","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna-Lena","family":"Leverin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malin","family":"Gustavsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carina","family":"Mallard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccarda","family":"Granata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Destefanis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Volante","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik","family":"Hagberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ezio","family":"Ghigo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u0308rgen","family":"Isgaard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071614183552600_R1","author":"Volpe","year":"2001"},{"key":"2020071614183552600_R2","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/S0140-6736(03)12658-X","article-title":"Origin and timing of brain lesions in term infants with neonatal encephalopathy.","volume":"361","author":"Cowan","year":"2003","journal-title":"Lancet"},{"key":"2020071614183552600_R3","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1136\/adc.64.7_Spec_No.953","article-title":"Magnetic resonance and near infrared spectroscopy for investigation of perinatal hypoxic-ischaemic brain injury.","volume":"64","author":"Wyatt","year":"1989","journal-title":"Arch Dis Child"},{"key":"2020071614183552600_R4","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/(SICI)1097-4695(19980915)36:4<455::AID-NEU1>3.0.CO;2-V","article-title":"Insulin-like growth factor-I prevents apoptosis in neurons after nerve growth factor withdrawal.","volume":"36","author":"Russell","year":"1998","journal-title":"J Neurobiol"},{"key":"2020071614183552600_R5","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1002\/(SICI)1097-4695(199912)41:4<540::AID-NEU9>3.0.CO;2-P","article-title":"Insulin-like growth factor-I prevents caspase-mediated apoptosis in Schwann cells.","volume":"41","author":"Delaney","year":"1999","journal-title":"J Neurobiol"},{"key":"2020071614183552600_R6","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1046\/j.1471-4159.1999.0730548.x","article-title":"Apoptotic cell death and caspase-3 activation induced by N-methyl-d-aspartate receptor antagonists and their prevention by insulin-like growth factor I.","volume":"73","author":"Takadera","year":"1999","journal-title":"J Neurochem"},{"key":"2020071614183552600_R7","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/sj.cdd.4400693","article-title":"IGF-I receptor activation and BCL-2 overexpression prevent early apoptotic events in human neuroblastoma.","volume":"7","author":"Golen","year":"2000","journal-title":"Cell Death Differ"},{"key":"2020071614183552600_R8","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1172\/JCI118416","article-title":"Insulin-like growth factor-1 is a potent neuronal rescue agent after hypoxic-ischemic injury in fetal lambs.","volume":"97","author":"Johnston","year":"1996","journal-title":"J Clin Invest"},{"key":"2020071614183552600_R9","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1203\/00006450-199903000-00005","article-title":"Possible protective role of growth hormone in hypoxia-ischemia in neonatal rats.","volume":"45","author":"Gustafson","year":"1999","journal-title":"Pediatr Res"},{"key":"2020071614183552600_R10","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1006\/nbdi.1999.0275","article-title":"BDNF blocks caspase-3 activation in neonatal hypoxia-ischemia.","volume":"7","author":"Han","year":"2000","journal-title":"Neurobiol Dis"},{"key":"2020071614183552600_R11","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/S0306-4522(01)00109-9","article-title":"Growth hormone as a neuronal rescue factor during recovery from CNS injury.","volume":"104","author":"Scheepens","year":"2001","journal-title":"Neuroscience"},{"key":"2020071614183552600_R12","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/S0006-8993(01)03148-1","article-title":"Neuroprotective effects of the N-terminal tripeptide of IGF1, glycine-proline-glutamate, in the immature rat brain after hypoxic-ischemic injury.","volume":"922","author":"Sizonenko","year":"2001","journal-title":"Brain Res"},{"key":"2020071614183552600_R13","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1128\/MCB.17.3.1595","article-title":"Antiapoptotic signalling by the insulin-like growth factor I receptor, phosphatidylinositol 3-kinase, and Akt.","volume":"17","author":"Kulik","year":"1997","journal-title":"Mol Cell Biol"},{"key":"2020071614183552600_R14","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0092-8674(00)80405-5","article-title":"Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery.","volume":"91","author":"Datta","year":"1997","journal-title":"Cell"},{"key":"2020071614183552600_R15","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1126\/science.282.5392.1318","article-title":"Regulation of cell death protease caspase-9 by phosphorylation.","volume":"282","author":"Cardone","year":"1998","journal-title":"Science"},{"key":"2020071614183552600_R16","doi-asserted-by":"crossref","first-page":"19929","DOI":"10.1074\/jbc.273.32.19929","article-title":"Role of glycogen synthase kinase-3 in the phosphatidylinositol 3-kinase\/Akt cell survival pathway.","volume":"273","author":"Pap","year":"1998","journal-title":"J Biol Chem"},{"key":"2020071614183552600_R17","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/S0092-8674(00)80595-4","article-title":"Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor.","volume":"96","author":"Brunet","year":"1999","journal-title":"Cell"},{"key":"2020071614183552600_R18","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/43474","article-title":"NF-\u03baB is a target for Akt in anti-apoptotic PDGF signaling.","volume":"401","author":"Romashkowa","year":"1999","journal-title":"Nature"},{"key":"2020071614183552600_R19","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1111\/j.1460-9568.2005.03982.x","article-title":"IGF-I neuroprotection in the immature brain after hypoxia-ischemia, involvement of Akt and GSK3\u03b2?","volume":"21","author":"Brywe","year":"2005","journal-title":"Eur J Neurosci"},{"key":"2020071614183552600_R20","first-page":"301","article-title":"Treatment with the GSK3B inhibitor Chir98025 decreases infarct size following MCAo.","volume":"34","author":"Kelly","year":"2003","journal-title":"Stroke"},{"key":"2020071614183552600_R21","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1073\/pnas.93.7.2719","article-title":"Regulation of mitochondrial pyruvate dehydrogenase activity by \u03c4 protein kinase I\/glycogen synthase kinase 3\u03b2 in brain.","volume":"93","author":"Hoshi","year":"1996","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614183552600_R22","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/27208","article-title":"Destabilization of \u03b2-catenin by mutations in presenilin-1 potentiates neuronal apoptosis.","volume":"395","author":"Zhang","year":"1998","journal-title":"Nature"},{"key":"2020071614183552600_R23","doi-asserted-by":"crossref","first-page":"7951","DOI":"10.1073\/pnas.122062299","article-title":"Direct, activating interaction between glycogen synthase kinase-3\u03b2 and p53 after DNA damage.","volume":"99","author":"Watcharasit","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614183552600_R24","doi-asserted-by":"crossref","first-page":"48872","DOI":"10.1074\/jbc.M305870200","article-title":"Glycogen synthase kinase-3\u03b2 (GSK3\u03b2) binds to and promotes the actions of p53.","volume":"278","author":"Watcharasit","year":"2003","journal-title":"J Biol Chem"},{"key":"2020071614183552600_R25","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1172\/JCI2169","article-title":"Caspase inhibitor affords neuroprotection with delayed administration in a rat model of neonatal hypoxic-ischemic brain injury.","volume":"101","author":"Cheng","year":"1998","journal-title":"J Clin Invest"},{"key":"2020071614183552600_R26","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1097\/00004647-200009000-00003","article-title":"Involvement of caspase-3 in cell death after hypoxia-ischemia declines during brain maturation.","volume":"20","author":"Hu","year":"2000","journal-title":"J Cereb Blood Flow Metab"},{"key":"2020071614183552600_R27","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1046\/j.1471-4159.2000.0750819.x","article-title":"Correlation between caspase-3 activation and three different markers of DNA damage in neonatal cerebral hypoxia-ischemia.","volume":"75","author":"Zhu","year":"2000","journal-title":"J Neurochem"},{"key":"2020071614183552600_R28","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1159\/000047087","article-title":"Caspase-3 activation after neonatal rat cerebral hypoxia-ischemia.","volume":"79","author":"Wang","year":"2001","journal-title":"Biol Neonate"},{"key":"2020071614183552600_R29","doi-asserted-by":"crossref","first-page":"30128","DOI":"10.1074\/jbc.M202931200","article-title":"Selective, reversible caspase-3 inhibitor is neuroprotective and reveals distinct pathways of cell death after neonatal hypoxic-ischemic brain injury.","volume":"277","author":"Han","year":"2002","journal-title":"J Biol Chem"},{"key":"2020071614183552600_R30","first-page":"159","article-title":"ERK activation protects against DNA damage and apoptosis in hyperoxic rat AEC2.","volume":"277","author":"Buckley","year":"1999","journal-title":"Am J Physiol"},{"key":"2020071614183552600_R31","doi-asserted-by":"crossref","first-page":"5308","DOI":"10.1128\/MCB.19.8.5308","article-title":"B-Raf inhibits programmed cell death downstream of cytochrome c release from mitochondria by activating the MEK\/ERK pathway.","volume":"19","author":"Erhardt","year":"1999","journal-title":"Mol Cell Biol"},{"key":"2020071614183552600_R32","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1042\/bj3330291","article-title":"The cellular response to oxidative stress: influences of mitogen-activated protein kinases signalling pathways on cell survival.","volume":"333","author":"Wang","year":"1998","journal-title":"Biochem J"},{"key":"2020071614183552600_R33","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1523\/JNEUROSCI.19-02-00664.1999","article-title":"A role for MAPK\/ERK in sympathetic neuron survival: protection against a p53-dependent, JNK-independent induction of apoptosis by cytosine arabinoside.","volume":"19","author":"Anderson","year":"1999","journal-title":"J Neurosci"},{"key":"2020071614183552600_R34","doi-asserted-by":"crossref","first-page":"5775","DOI":"10.1523\/JNEUROSCI.20-15-05775.2000","article-title":"BDNF protects the neonatal brain from hypoxic-ischemic injury in vivo via the ERK pathway.","volume":"20","author":"Han","year":"2000","journal-title":"J Neurosci"},{"key":"2020071614183552600_R35","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1530\/eje.0.1360445","article-title":"Growth hormone-releasing peptides.","volume":"136","author":"Ghigo","year":"1997","journal-title":"Eur J Endocrinol"},{"key":"2020071614183552600_R36","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0167-0115(03)00117-4","article-title":"Ghrelin, a novel growth hormone-releasing peptide, in the treatment of chronic heart failure.","volume":"114","author":"Nagaya","year":"2003","journal-title":"Regul Pept"},{"key":"2020071614183552600_R37","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/45230","article-title":"Ghrelin is a growth-hormone-releasing acylated peptide from stomach.","volume":"402","author":"Kojima","year":"1999","journal-title":"Nature"},{"key":"2020071614183552600_R38","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/35051587","article-title":"A role for ghrelin in the central regulation of feeding.","volume":"409","author":"Nakazato","year":"2001","journal-title":"Nature"},{"key":"2020071614183552600_R39","doi-asserted-by":"crossref","first-page":"4024","DOI":"10.1210\/endo.140.9.6948","article-title":"Growth hormone independent cardioprotective effects of hexarelin in the rat.","volume":"140","author":"Locatelli","year":"1999","journal-title":"Endocrinology"},{"key":"2020071614183552600_R40","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1210\/endo.141.1.7249","article-title":"The growth hormone secretagogue hexarelin improves cardiac function in rats after experimental myocardial infarction.","volume":"141","author":"Tivesten A\u030a, Bollano","year":"2000","journal-title":"Endocrinology"},{"key":"2020071614183552600_R41","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1083\/jcb.200207165","article-title":"Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1\/2 and PI 3-kinase\/AKT.","volume":"159","author":"Baldanzi","year":"2002","journal-title":"J Cell Biol"},{"key":"2020071614183552600_R42","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/ana.410090206","article-title":"The influence of immaturity on hypoxic-ischemic brain damage in the rat.","volume":"9","author":"Rice","year":"1981","journal-title":"Ann Neurol"},{"key":"2020071614183552600_R43","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1651-2227.1997.tb18353.x","article-title":"Hypoxia-ischemia model in 7 day old rat: possibilities and shortcomings.","volume":"442","author":"Hagberg","year":"1997","journal-title":"Acta Paediatr Suppl"},{"key":"2020071614183552600_R44","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1203\/00006450-199301000-00013","article-title":"Frequent episodes of brief ischemia sensitize the fetal sheep brain to neuronal loss and induce striatal injury.","volume":"33","author":"Mallard","year":"1993","journal-title":"Pediatr Res"},{"key":"2020071614183552600_R45","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1097\/00004647-199802000-00014","article-title":"Temporal changes of regional glucose use, blood flow, and microtubule-associated protein 2 immunostaining after hypoxia-ischemia in the immature rat brain.","volume":"18","author":"Gilland","year":"1998","journal-title":"J Cereb Blood Flow Metab"},{"key":"2020071614183552600_R46","doi-asserted-by":"crossref","first-page":"5910","DOI":"10.1523\/JNEUROSCI.22-14-05910.2002","article-title":"Interleukin-18 involvement in hypoxic-ischemic brain injury.","volume":"22","author":"Hedtja\u0308rn","year":"2002","journal-title":"J Neurosci"},{"key":"2020071614183552600_R47","doi-asserted-by":"crossref","first-page":"F3","DOI":"10.1136\/fn.74.1.F3","article-title":"Posthypoxic cooling of neonatal rats provides protection against brain injury","volume":"74","author":"Thoresen","year":"1996","journal-title":"Arch Dis Child"},{"key":"2020071614183552600_R48","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1006\/nbdi.2002.0482","article-title":"Akt phosphorylation and neuronal survival after traumatic brain injury in mice.","volume":"9","author":"Noshita","year":"2002","journal-title":"Neurobiol Dis"},{"key":"2020071614183552600_R49","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/0003-2697(80)90024-X","article-title":"An absolute method for protein determination based on a difference in absorbance at 235 and 280 nm.","volume":"109","author":"Whitaker","year":"1980","journal-title":"Anal Biochem"},{"key":"2020071614183552600_R50","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/0165-3806(93)90008-X","article-title":"Localization and ontogeny of growth hormone receptor gene expression in the central nervous system.","volume":"74","author":"Lobie","year":"1993","journal-title":"Dev Brain Res"},{"key":"2020071614183552600_R51","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/S0169-328X(99)00051-0","article-title":"Alterations in the neural growth hormone axis following hypoxic-ischemic brain injury.","volume":"68","author":"Scheepens","year":"1999","journal-title":"Brain Res Mol Brain Res"},{"key":"2020071614183552600_R52","doi-asserted-by":"crossref","first-page":"4113","DOI":"10.1210\/en.2002-220261","article-title":"Growth hormone (GH) and GH-releasing peptide-6 increase brain insulin-like growth factor-I expression and activate intracellular signaling pathways involved in neuroprotection.","volume":"143","author":"Frago","year":"2002","journal-title":"Endocrinology"},{"key":"2020071614183552600_R53","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/0306-4522(92)90193-6","article-title":"Cellular pattern of type-I insulin-like growth factor gene expression during maturation of the rat brain: comparison with insulin-like growth factors I and II.","volume":"46","author":"Bondy","year":"1992","journal-title":"Neuroscience"},{"key":"2020071614183552600_R54","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/jcbfm.1993.79","article-title":"The effects of IGF-1 treatment after hypoxic-ischemic brain injury in adult rats.","volume":"13","author":"Guan","year":"1993","journal-title":"J Cereb Blood Flow Metab"},{"key":"2020071614183552600_R55","first-page":"3294","article-title":"Neutral endopeptidase inhibits neuropeptide-mediated transactivation of the insulin-like growth factor receptor-Akt cell survival pathway.","volume":"61","author":"Sumitomo","year":"2001","journal-title":"Cancer Res"},{"key":"2020071614183552600_R56","doi-asserted-by":"crossref","first-page":"2978","DOI":"10.1210\/en.2004-0029","article-title":"Transactivation of the insulin-like growth factor-I receptor by angiotensin II mediates downstream signaling from the angiotensin II type 1 receptor to phosphatidylinositol 3-kinase.","volume":"145","author":"Zahradka","year":"2004","journal-title":"Endocrinology"},{"key":"2020071614183552600_R57","doi-asserted-by":"crossref","first-page":"H1063","DOI":"10.1152\/ajpheart.00648.2003","article-title":"Hexarelin protects rat cardiomyocytes from angiotensin II-induced apoptosis in vitro","volume":"286","author":"Pang","year":"2004","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2020071614183552600_R58","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/378785a0","article-title":"Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B.","volume":"378","author":"Cross","year":"1995","journal-title":"Nature"},{"key":"2020071614183552600_R59","doi-asserted-by":"crossref","first-page":"7713","DOI":"10.1074\/jbc.272.12.7713","article-title":"Regulation of protein kinase B and glycogen synthase kinase-3 by insulin and B-adrenergic agonists in rat epididymal fat cells.","volume":"272","author":"Moule","year":"1997","journal-title":"J Biol Chem"},{"key":"2020071614183552600_R60","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/S1471-4914(01)02266-3","article-title":"Glycogen synthase kinase 3: an emerging therapeutic target.","volume":"8","author":"Eldar-Finkelman","year":"2002","journal-title":"Trends Mol Med"},{"key":"2020071614183552600_R61","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1046\/j.1471-4159.2001.t01-1-00251.x","article-title":"Selective small-molecule inhibitors of glycogen synthase kinase-3 activity protect primary neurones from death.","volume":"77","author":"Cross","year":"2001","journal-title":"J Neurochem"},{"key":"2020071614183552600_R62","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1097\/00004647-200204000-00006","article-title":"Role of caspase-3 activation in cerebral ischemia-induced neurodegeneration in adult and neonatal brain.","volume":"22","author":"Gill","year":"2002","journal-title":"J Cereb Blood Flow Metab"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/146\/11\/4665\/9020893\/endo4665.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/146\/11\/4665\/9020893\/endo4665.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T01:55:23Z","timestamp":1594950923000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/146\/11\/4665\/2499763"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,11,1]]},"references-count":62,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2005,11,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2005-0389","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,11,1]]}}}