Ghrelin receptor signaling is not required for glucocorticoid-induced obesity in female mice

in Journal of Endocrinology
Authors:
Zachary Silver Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada

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https://orcid.org/0000-0002-3064-6182
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Sam Abbott-Tate Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada

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Lindsay Hyland Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada

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Frances Sherratt Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada

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Barbara Woodside Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada

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Alfonso Abizaid Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada

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Correspondence should be addressed to A Abizaid: alfonso_abizaid@carleton.ca
DOI:
https://doi.org/10.1530/JOE-20-0579
Volume/Issue:
Volume 250: Issue 2
Article Type:
Research Article
Page Range:
37–48
Online Publication Date:
28 Jun 2021
Copyright:
© Society for Endocrinology 2021
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Chronic exposure to high circulating glucocorticoid or ghrelin concentrations increases food intake, weight gain and adiposity, suggesting that ghrelin could contribute to the metabolic effects of chronic glucocorticoids. In male mice, however, blocking ghrelin receptor (GHSR) signaling increased the weight gain and adiposity induced by chronic corticosterone (CORT), rather than attenuating them. In the current study, we investigated the role of GHSR signaling in the metabolic effects of chronic exposure to high circulating CORT in female mice. To do this, female WT and GHSR KO mice were treated with either CORT in a 1% ethanol (EtOH) solution or 1% EtOH alone in their drinking water for 32 days (n = 5–8/group). Body weight, food, and water intake as well as vaginal cyclicity were assessed daily. As expected, CORT treatment-induced significant increases in body weight, food intake, adiposity and also impaired glucose tolerance. In contrast to results observed in male mice, WT and GHSR KO female mice did not differ on any of these parameters. Neither plasma levels of ghrelin, LEAP-2, the endogenous GHSR antagonist produced by the liver, nor their ratio were altered by chronic glucocorticoid exposure. In addition, CORT treatment disrupted vaginal cyclicity, produced a reduction in sucrose consumption and increased locomotor activity regardless of genotype. Chronic CORT also decreased exploration in WT but not GHSR KO mice. Collectively, these data suggest that most metabolic, endocrine, reproductive and behavioral effects of chronic CORT exposure are independent of GHSR signaling in female mice.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© Society for Endocrinology 2021
Page(s):
12
Article Type:
Research Article
Received Date:
13 May 2021
Accepted Date:
01 Jun 2021
Print Publication Date:
01 Aug 2021
Online Publication Date:
28 Jun 2021
Keywords:
ghrelin; GHSR; corticosterone; obesity; glucose tolerance; metabolism

  • Abizaid A 2019 Stress and obesity: the ghrelin connection. Journal of Neuroendocrinology 31 e12693. (https://doi.org/10.1111/jne.12693)

  • Berger S, Gureczny S, Reisinger SN, Horvath O & Pollak DD 2019 Effect of chronic corticosterone treatment on depression-like behavior and sociability in female and male C57BL/6N mice. Cells 8 1018. (https://doi.org/10.3390/cells8091018)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Bertagna X, Guignat L, Groussin L & Bertherat J 2009 Cushing’s disease. Best Practice and Research. Clinical Endocrinology and Metabolism 23 607–623. (https://doi.org/10.1016/j.beem.2009.06.001)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Boscaro M, Barzon L, Fallo F & Sonino N 2001 Cushing’s syndrome. Lancet: Elsevier Limited 357 783–791. (https://doi.org/10.1016/S0140-6736(0004172-6)

  • Bowles NP, Hill MN, Bhagat SM, Karatsoreos IN, Hillard CJ & McEwen BS 2012 Chronic, noninvasive glucocorticoid administration suppresses limbic endocannabinoid signaling in mice. Neuroscience 204 83–89. (https://doi.org/10.1016/j.neuroscience.2011.08.048)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Brummelte S & Galea LAM 2010 Chronic corticosterone during pregnancy and postpartum affects maternal care, cell proliferation and depressive-like behavior in the dam. Hormones and Behavior 58 769–779. (https://doi.org/10.1016/j.yhbeh.2010.07.012)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Burgess LH & Handa RJ 1992 Chronic estrogen-induced alterations in adrenocorticotropin and corticosterone secretion, and glucocorticoid receptor-mediated functions in female rats. Endocrinology 131 1261–1269. (https://doi.org/10.1210/endo.131.3.1324155)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Caligioni CS 2009 Assessing reproductive status/stages in mice. Current Protocols in Neuroscience 4 8 Appendix 4:Appendix 4I. (https://doi.org/10.1002/0471142301.nsa04is48)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chuang JC, Perello M, Sakata I, Osborne-Lawrence S, Savitt JM, Lutter M & Zigman JM 2011 Ghrelin mediates stress-induced food-reward behavior in mice. Journal of Clinical Investigation 121 2684–2692. (https://doi.org/10.1172/JCI57660)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Clegg DJ, Brown LM, Zigman JM, Kemp CJ, Strader AD, Benoit SC, Woods SC, Mangiaracina M & Geary N 2007 Estradiol-dependent decrease in the orexigenic potency of ghrelin in female rats. Diabetes 56 1051–1058. (https://doi.org/10.2337/db06-0015)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Clore JN & Thurby-Hay L 2009 Glucocorticoid-induced hyperglycemia. Endocrine Practice 15 469–474. (https://doi.org/10.4158/EP08331.RAR)

  • Cui A, Fan H, Zhang Y, Zhang Y, Niu D, Liu S, Liu Q, Ma W, Shen Z, Shen L, et al.2019 Dexamethasone-induced Krüppel-like factor 9 expression promotes hepatic gluconeogenesis and hyperglycemia. Journal of Clinical Investigation 129 2266–2278. (https://doi.org/10.1172/JCI66062)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Dallman MF 2007 Modulation of stress responses: how we cope with excess glucocorticoids. Experimental Neurology 206 179–182. (https://doi.org/10.1016/j.expneurol.2007.06.002)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Dallman MF 2010 Stress-induced obesity and the emotional nervous system. Trends in Endocrinology and Metabolism 21 159–165. (https://doi.org/10.1016/j.tem.2009.10.004)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • David DJ, Samuels BA, Rainer Q, Wang JW, Marsteller D, Mendez I, Drew M, Craig DA, Guiard BP, Guilloux JP, et al.2009 Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety/depression. Neuron 62 479–493. (https://doi.org/10.1016/j.neuron.2009.04.017)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Debons AF, Das KC, Fuhr B & Siclari E 1983 Anorexia after adrenalectomy in gold thioglucose-treated obese mice. Endocrinology 112 1847–1851. (https://doi.org/10.1210/endo-112-5-1847)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Demuyser T, Bentea E, Deneyer L, Albertini G, Massie A & Smolders I 2016 Disruption of the HPA-axis through corticosterone-release pellets induces robust depressive-like behavior and reduced BDNF levels in mice. Neuroscience Letters 626 119–125. (https://doi.org/10.1016/j.neulet.2016.05.026)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Dieterich A, Srivastava P, Sharif A, Stech K, Floeder J, Yohn SE & Samuels BA 2019 Chronic corticosterone administration induces negative valence and impairs positive valence behaviors in mice. Translational Psychiatry 9 337. (https://doi.org/10.1038/s41398-019-0674-4)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ding H, Cui XY, Cui SY, Ye H, Hu X, Zhao HL, Liu YT & Zhang YH 2018 Depression-like behaviors induced by chronic corticosterone exposure via drinking water: time-course analysis. Neuroscience Letters 687 202–206. (https://doi.org/10.1016/j.neulet.2018.09.059)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Esser N, Legrand-Poels S, Piette J, Scheen AJ & Paquot N 2014 Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Research and Clinical Practice 105 141–150. (https://doi.org/10.1016/j.diabres.2014.04.006)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Fernández-Fernández R, Tena-Sempere M, Navarro VM, Barreiro ML, Castellano JM, Aguilar E & Pinilla L 2005 Effects of ghrelin upon gonadotropin-releasing hormone and gonadotropin secretion in adult female rats: in vivo and in vitro Studies. Neuroendocrinology 82 245–255. (https://doi.org/10.1159/000092753)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Forbes S, Li XF, Kinsey-Jones J & O’Byrne K 2009 Effects of ghrelin on kisspeptin mRNA expression in the hypothalamic medial preoptic area and pulsatile luteinising hormone secretion in the female rat. Neuroscience Letters 460 143–147. (https://doi.org/10.1016/j.neulet.2009.05.060)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ge X, Yang H, Bednarek MA, Galon-Tilleman H, Chen P, Chen M, Lichtman JS, Wang Y, Dalmas O, Yin Y, et al.2018 LEAP2 is an endogenous antagonist of the ghrelin receptor. Cell Metabolism 27 461–469.e6. (https://doi.org/10.1016/j.cmet.2017.10.016)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gore AC, Attardi B & DeFranco DB 2006 Glucocorticoid repression of the reproductive axis: effects on GnRH and gonadotropin subunit mRNA levels. Molecular and Cellular Endocrinology 256 40–48. (https://doi.org/10.1016/j.mce.2006.06.002)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gourley SL, Wu FJ, Kiraly DD, Ploski JE, Kedves AT, Duman RS & Taylor JR 2008 Regionally specific regulation of ERK MAP kinase in a model of antidepressant-sensitive chronic depression. Biological Psychiatry 63 353–359. (https://doi.org/10.1016/j.biopsych.2007.07.016)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Guilloux JP, Seney M, Edgar N & Sibille E 2011 Integrated behavioral z-scoring increases the sensitivity and reliability of behavioral phenotyping in mice: relevance to emotionality and sex. Journal of Neuroscience Methods 197 21–31. (https://doi.org/10.1016/j.jneumeth.2011.01.019)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gupta D, Chuang JC, Mani BK, Shankar K, Rodriguez JA, Osborne-Lawrence S, Metzger NP & Zigman JM 2019 β1-adrenergic receptors mediate plasma acyl-ghrelin elevation and depressive-like behavior induced by chronic psychosocial stress. Neuropsychopharmacology 44 1319–1327. (https://doi.org/10.1038/s41386-019-0334-7)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hay RE, Edwards A, Klein M, Hyland L, MacDonald D, Karatsoreos I, Hill MN & Abizaid A 2020 Ghrelin receptor signaling is not required for glucocorticoid-induced obesity in male mice. Endocrinology 161 1–16. (https://doi.org/10.1210/endocr/bqz023)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hewitt BM, Yap MH, Hodson-Tole EF, Kennerley AJ, Sharp PS & Grant RA 2018 A novel automated rodent tracker (ART), demonstrated in a mouse model of amyotrophic lateral sclerosis. Journal of Neuroscience Methods 300 147–156. (https://doi.org/10.1016/j.jneumeth.2017.04.006)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hill JL, Solomon MB, Nguyen ET, Caldwell JL, Wei Y & Foster MT 2020 Glucocorticoids regulate adipose tissue protein concentration in a depot- and sex-specific manner. Stress 23 243–247. (https://doi.org/10.1080/10253890.2019.1658736)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kaikaew K, Steenbergen J, van Dijk TH, Grefhorst A & Visser JA 2019 Sex difference in corticosterone-induced insulin resistance in mice. Endocrinology 160 2367–2387. (https://doi.org/10.1210/en.2019-00194)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Karatsoreos IN, Bhagat SM, Bowles NP, Weil ZM, Pfaff DW & McEwen BS 2010 Endocrine and physiological changes in response to chronic corticosterone: a potential model of the metabolic syndrome in mouse. Endocrinology 151 2117–2127. (https://doi.org/10.1210/en.2009-1436)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kluge M, Schüssler P, Schmidt D, Uhr M & Steiger A 2012 Ghrelin suppresses secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in women. Journal of Clinical Endocrinology and Metabolism 97 E448–E451. (https://doi.org/10.1210/jc.2011-2607)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kristenssson E, Sundqvist M, Astin M, Kjerling M, Mattsson H, Dornonville de la Cour C, Håkanson R & Lindström E 2006 Acute psychological stress raises plasma ghrelin in the rat. Regulatory Peptides 134 114–117. (https://doi.org/10.1016/j.regpep.2006.02.003)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kuo T, McQueen A, Chen TC & Wang JC 2015 Regulation of glucose homeostasis by glucocorticoids. Advances in Experimental Medicine and Biology 872 99–126. (https://doi.org/10.1007/978-1-4939-2895-8_5)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kvarta MD, Bradbrook KE, Dantrassy HM, Bailey AM & Thompson SM 2015 Corticosterone mediates the synaptic and behavioral effects of chronic stress at rat hippocampal temporoammonic synapses. Journal of Neurophysiology 114 1713–1724. (https://doi.org/10.1152/jn.00359.2015)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Li PS & Wagner WC 1983 In vivo and in vitro studies on the effect of adrenocorticotropic hormone or cortisol on the pituitary response to gonadotropin releasing hormone. Biology of Reproduction 29 25–37. (https://doi.org/10.1095/biolreprod29.1.25)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Löfgren M, Holmberg E, Bäckström T, Egecioglu E & Dickson SL 2019 The additive effect of allopregnanolone on ghrelin’s orexigenic effect in rats. Neuropeptides 76 101937. (https://doi.org/10.1016/j.npep.2019.101937)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Luo E, Stephens SBZ, Chaing S, Munaganuru N, Kauffman AS & Breen KM 2016 Corticosterone blocks ovarian cyclicity and the LH surge via decreased kisspeptin neuron activation in female mice. Endocrinology 157 1187–1199. (https://doi.org/10.1210/en.2015-1711)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lutter M, Sakata I, Osborne-Lawrence S, Rovinsky SA, Anderson JG, Jung S, Birnbaum S, Yanagisawa M, Elmquist JK, Nestler EJ, et al.2008 The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress. Nature Neuroscience 11 752–753. (https://doi.org/10.1038/nn.2139)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Mani BK, Puzziferri N, He Z, Rodriguez JA, Osborne-Lawrence S, Metzger NP, Chhina N, Gaylinn B, Thorner MO, Louise Thomas EL, et al.2019 LEAP2 changes with body mass and food intake in humans and mice. Journal of Clinical Investigation 129 3909–3923. (https://doi.org/10.1172/JCI125332)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • McGovern-Gooch KR, Rodrigues T, Darling JE, Sieburg MA, Abizaid A & Hougland JL 2016 Ghrelin octanoylation is completely stabilized in biological samples by alkyl fluorophosphonates. Endocrinology 157 4330–4338. (https://doi.org/10.1210/en.2016-1657)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Mekiri M, Gardier AM, David DJ & Guilloux JP 2017 Chronic corticosterone administration effects on behavioral emotionality in female C57BL6 mice. Experimental and Clinical Psychopharmacology 25 94–104. (https://doi.org/10.1037/pha0000112)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Meshkani R & Adeli K 2009 Hepatic insulin resistance, metabolic syndrome and cardiovascular disease. Clinical Biochemistry 42 1331–1346. (https://doi.org/10.1016/j.clinbiochem.2009.05.018)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K & Matsukura S 2001 A role for ghrelin in the central regulation of feeding. Nature 409 194–198. (https://doi.org/10.1038/35051587)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Paccola CC, Resende CG, Stumpp T, Miraglia SM & Cipriano I 2018 The rat estrous cycle revisited: a quantitative and qualitative analysis. Animal Reproduction 10 677–683.

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Palanza P 2001 Animal models of anxiety and depression: how are females different? Neuroscience and Biobehavioral Reviews 25 219–233. (https://doi.org/10.1016/S0149-7634(0100010-0)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Patterson ZR, Khazall R, MacKay H, Anisman H & Abizaid A 2013 Central ghrelin signaling mediates the metabolic response of C57BL/6 male mice to chronic social defeat stress. Endocrinology 154 1080–1091. (https://doi.org/10.1210/en.2012-1834)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Proulx K, Vahl TP, Drazen DL, Woods SC & Seeley RJ 2005 The effect of adrenalectomy on ghrelin secretion and orexigenic action. Journal of Neuroendocrinology 17 445–451. (https://doi.org/10.1111/j.1365-2826.2005.01322.x)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rafacho A, Ortsäter H, Nadal A & Quesada I 2014 Glucocorticoid treatment and endocrine pancreas function: implications for glucose homeostasis, insulin resistance and diabetes. Journal of Endocrinology 223 R49–R62. (https://doi.org/10.1530/JOE-14-0373)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rebuffé-Scrive M, Walsh UA, McEwen B & Rodin J 1992 Effect of chronic stress and exogenous glucocorticoids on regional fat distribution and metabolism. Physiology and Behavior 52 583–590. (https://doi.org/10.1016/0031-9384(9290351-2)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ritchie SA & Connell JMC 2007 The link between abdominal obesity, metabolic syndrome and cardiovascular disease. Nutrition, Metabolism, and Cardiovascular Diseases 17 319–326. (https://doi.org/10.1016/j.numecd.2006.07.005)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rivier C & Rivest S 1991 Effect of stress on the activity of the hypothalamic-pituitary-gonadal axis: peripheral and central mechanisms. Biology of Reproduction 45 523–532. (https://doi.org/10.1095/biolreprod45.4.523)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rosmond R 2005 Role of stress in the pathogenesis of the metabolic syndrome. Psychoneuroendocrinology 30 1–10. (https://doi.org/10.1016/j.psyneuen.2004.05.007).

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sakurazawa N, Mano-Otagiri A, Nemoto T & Shibasaki T 2013 Effects of intracerebroventricular ghrelin on food intake and Fos expression in the arcuate nucleus of the hypothalamus in female rats vary with estrous cycle phase. Neuroscience Letters 541 204–208. (https://doi.org/10.1016/j.neulet.2013.02.006).

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Savontaus E, Conwell IM & Wardlaw SL 2002 Effects of adrenalectomy on AGRP, POMC, NPY and CART gene expression in the basal hypothalamus of fed and fasted rats. Brain Research 958 130–138. (https://doi.org/10.1016/S0006-8993(0203674-0).

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sefton C, Harno E, Davies A, Small H, Allen TJ, Wray JR, Lawrence CB, Coll AP & White A 2016 Elevated hypothalamic glucocorticoid levels are associated with obesity and hyperphagia in male mice. Endocrinology 157 4257–4265. (https://doi.org/10.1210/en.2016-1571)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Shimizu H, Arima H, Watanabe M, Goto M, Banno R, Sato I, Ozaki N, Nagasaki H & Oiso Y 2008 Glucocorticoids increase neuropeptide Y and agouti-related peptide gene expression via adenosine monophosphate-activated protein kinase signaling in the arcuate nucleus of rats. Endocrinology 149 4544–4553. (https://doi.org/10.1210/en.2008-0229)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sobrino Crespo C, Perianes Cachero A, Puebla, Jiménez L, Barrios V & Arilla Ferreiro E 2014 Peptides and food intake. Frontiers in Endocrinology 5 58. (https://doi.org/10.3389/fendo.2014.00058)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sominsky L, Hodgson DM, McLaughlin EA, Smith R, Wall HM & Spencer SJ 2017 Linking stress and infertility: a novel role for ghrelin. Endocrine Reviews 38 432–467. (https://doi.org/10.1210/ER.2016-1133)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sowers JR 2007 Metabolic risk factors and renal disease. Kidney International 71 719–720. (https://doi.org/10.1038/sj.ki.5002006)

  • Spencer SJ, Xu L, Clarke MA, Lemus M, Reichenbach A, Geenen B, Kozicz T & Andrews ZB 2012 Ghrelin regulates the hypothalamic-pituitary-adrenal axis and restricts anxiety after acute stress. Biological Psychiatry 72 457–465. (https://doi.org/10.1016/j.biopsych.2012.03.010)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Steffensen C, Bak AM, Zøylner Rubeck KZ & Jørgensen JOL 2010 Epidemiology of Cushing’s syndrome. Neuroendocrinology 92(Supplement 1) 1–5. (https://doi.org/10.1159/000314297)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sterner EY & Kalynchuk LE 2010 Behavioral and neurobiological consequences of prolonged glucocorticoid exposure in rats: relevance to depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry 34 777–790. (https://doi.org/10.1016/j.pnpbp.2010.03.005)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Stopa LRS, de Souza CF, Santos GF, Martins AB, Ferreira RN, de Andrade FG, Leite CM, Zaia DAM, Zaia CTBV & Uchoa ET 2019 Sex differences in glucocorticoids-induced anabolic effects in rats. Physiology and Behavior 209 112587. (https://doi.org/10.1016/j.physbeh.2019.112587)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Tang XN, Liebeskind DS & Towfighi A 2017 The role of diabetes, obesity, and metabolic syndrome in stroke. Seminars in Neurology 37 267–273. (https://doi.org/10.1055/s-0037-1603753)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Tschop M, Smiley DL & Heiman ML 2000 Ghrelin induces adiposity in rodents. Nature 407 908–913. (https://doi.org/10.1038/35038090)

  • Tschöp M, Wawarta R, Riepl RL, Friedrich S, Bidlingmaier M, Landgraf R & Folwaczny C 2001 Post-prandial decrease of circulating human ghrelin levels. Journal of Endocrinological Investigation 24 RC19–RC21. (https://doi.org/10.1007/BF03351037)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Viau V & Meaney MJ 1991 Variations in the hypothalamic-pituitary-adrenal response to stress during the estrous cycle in the rat. Endocrinology 129 2503–2511. (https://doi.org/10.1210/endo-129-5-2503)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Vulliémoz NR, Xiao E, Xia-Zhang L, Germond M, Rivier J & Ferin M 2004 Decrease in luteinizing hormone pulse frequency during a five-hour peripheral ghrelin infusion in the ovariectomized Rhesus Monkey. Journal of Clinical Endocrinology and Metabolism 89 5718–5723. (https://doi.org/10.1210/jc.2004-1244)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Whirledge S & Cidlowski JA 2017 Glucocorticoids and reproduction: traffic control on the road to reproduction. Trends in Endocrinology and Metabolism 28 399–415. (https://doi.org/10.1016/j.tem.2017.02.005)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • White BD, Dean RG & Martin RJ 1990 Adrenalectomy decreases neuropeptide Y mRNA levels in the arcuate nucleus. Brain Research Bulletin 25 711–715. (https://doi.org/10.1016/0361-9230(9090047-4)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wisialowski T, Parker R, Preston E, Sainsbury A, Kraegen E, Herzog H & Cooney G 2000 Adrenalectomy reduces neuropeptide Y-induced insulin release and NPY receptor expression in the rat ventromedial hypothalamus. Journal of Clinical Investigation 105 1253–1259. (https://doi.org/10.1172/JCI8695)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wray JR, Davies A, Sefton C, Allen TJ, Adamson A, Chapman P, Lam BYH, Yeo GSH, Coll AP, Harno E, et al.2019 Global transcriptomic analysis of the arcuate nucleus following chronic glucocorticoid treatment. Molecular Metabolism 26 5–17. (https://doi.org/10.1016/j.molmet.2019.05.008)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA & Bloom SR 2001 Ghrelin enhances appetite and increases food intake in humans. Journal of Clinical Endocrinology and Metabolism 86 5992. (https://doi.org/10.1210/jcem.86.12.8111)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zigman JM, Nakano Y, Coppari R, Balthasar N, Marcus JN, Lee CE, Jones JE, Deysher AE, Waxman AR, White RD, et al.2005 Mice lacking ghrelin receptors resist the development of diet-induced obesity. Journal of Clinical Investigation 115 3564–3572. (https://doi.org/10.1172/JCI26002)

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