{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe provided body of literature offers in‐depth analyses of growth hormone (GH) signaling through its receptor (GHR) and the downstream effectors that regulate a wide array of physiological processes—from metabolism and tissue growth to regeneration, immune modulation, and aging. These studies, employing whole‐body, tissue‐specific, and inducible knockout models (e.g., in liver, fat, muscle, and brain), delineate how alterations in GHR‐mediated pathways (including JAK/STAT, IGF‑I, mTOR, and others) affect insulin sensitivity, adiposity, bone acquisition, and even lifespan. Notably, however, none of the examined abstracts make any mention of SMIM40, nor do they provide evidence that links this protein to any function within the GH signaling cascade or its systemic outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nWithin the context of these comprehensive evaluations of GH and GHR biology—ranging from studies of GHR cleavage and tissue‐specific ablation (e.g., in muscle, adipose, and macrophages) to investigations into liver regeneration, reproductive function, and the interplay with metabolic and stress response pathways—the role of small integral membrane proteins (which, by name, would include SMIM40) could be hypothesized as potential modulators of receptor localization or signal transduction. However, none of these abstracts present data regarding SMIM40. Instead, they consistently focus on classical components of the GH/IGF‑I axis, providing little to no insight into whether SMIM40 interacts with, regulates, or is regulated by these pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "35"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn summary, while the extensive investigations summarized above underscore the critical influence of GH/GHR signaling on diverse biological functions—including metabolic regulation, tissue development and regeneration, and lifespan extension—they do not provide any direct information regarding SMIM40. Its function within these pathways, if any, remains undefined in the current literature. Future studies will be required to determine whether SMIM40, as a small integral membrane protein, may have regulatory or ancillary roles in modulating GH receptor signaling or cellular responses to GH. Until such data are available, SMIM40 cannot be conclusively linked to the well‐documented actions of GH presented in these studies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "36", "end_ref": "50"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yuxiang Sun, Pei Wang, Hui Zheng, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Deletion, but not antagonism, of the mouse growth hormone receptor results in severely decreased body weights, insulin, and insulin-like growth factor I levels and increased life span."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2003-0374"}], "href": "https://doi.org/10.1210/en.2003-0374"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12933651"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12933651"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Michael S Bonkowski, Juliana S Rocha, Michal M Masternak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeted disruption of growth hormone receptor interferes with the beneficial actions of calorie restriction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0600161103"}], "href": "https://doi.org/10.1073/pnas.0600161103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16682650"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16682650"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yong Fan, Ram K Menon, Pinchas Cohen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Liver-specific deletion of the growth hormone receptor reveals essential role of growth hormone signaling in hepatic lipid metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.014308"}], "href": "https://doi.org/10.1074/jbc.M109.014308"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19460757"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19460757"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Khalid A Al-Regaiey, Michal M Masternak, Michael Bonkowski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long-lived growth hormone receptor knockout mice: interaction of reduced insulin-like growth factor i/insulin signaling and caloric restriction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2004-1120"}], "href": "https://doi.org/10.1210/en.2004-1120"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15498882"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15498882"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jun-Li Liu, Karen T Coschigano, Katie Robertson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disruption of growth hormone receptor gene causes diminished pancreatic islet size and increased insulin sensitivity in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Endocrinol Metab (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpendo.00423.2003"}], "href": "https://doi.org/10.1152/ajpendo.00423.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15138153"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15138153"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Mahendra D Mavalli, Douglas J DiGirolamo, Yong Fan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct growth hormone receptor signaling modes regulate skeletal muscle development and insulin sensitivity in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI42447"}], "href": "https://doi.org/10.1172/JCI42447"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20921627"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20921627"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Edward O List, Darlene E Berryman, Kevin Funk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Liver-specific GH receptor gene-disrupted (LiGHRKO) mice have decreased endocrine IGF-I, increased local IGF-I, and altered body size, body composition, and adipokine profiles."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2013-2086"}], "href": "https://doi.org/10.1210/en.2013-2086"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24517230"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24517230"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jennifer E Rowland, Agnieszka M Lichanska, Linda M Kerr, et al. "}, {"type": "b", "children": [{"type": "t", "text": "In vivo analysis of growth hormone receptor signaling domains and their associated transcripts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.25.1.66-77.2005"}], "href": "https://doi.org/10.1128/MCB.25.1.66-77.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15601831"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15601831"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Edward O List, Darlene E Berryman, Kevin Funk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of GH in adipose tissue: lessons from adipose-specific GH receptor gene-disrupted mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2012-1330"}], "href": "https://doi.org/10.1210/me.2012-1330"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23349524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23349524"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Emil Egecioglu, Mikael Bjursell, Anna Ljungberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Growth hormone receptor deficiency results in blunted ghrelin feeding response, obesity, and hypolipidemia in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Endocrinol Metab (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpendo.00181.2005"}], "href": "https://doi.org/10.1152/ajpendo.00181.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16174655"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16174655"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Yingjie Wu, Chengyu Liu, Hui Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Growth hormone receptor regulates β cell hyperplasia and glucose-stimulated insulin secretion in obese mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI45027"}], "href": "https://doi.org/10.1172/JCI45027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21555853"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21555853"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Jose Cordoba-Chacon, Neena Majumdar, Edward O List, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Growth Hormone Inhibits Hepatic De Novo Lipogenesis in Adult Mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db15-0370"}], "href": "https://doi.org/10.2337/db15-0370"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26015548"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26015548"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Yuesheng Li, Joanne R Knapp, John J Kopchick "}, {"type": "b", "children": [{"type": "t", "text": "Enlargement of interscapular brown adipose tissue in growth hormone antagonist transgenic and in growth hormone receptor gene-disrupted dwarf mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Biol Med (Maywood) (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/153537020322800212"}], "href": "https://doi.org/10.1177/153537020322800212"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12563029"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12563029"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Olga Spadaro, Emily L Goldberg, Christina D Camell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Growth Hormone Receptor Deficiency Protects against Age-Related NLRP3 Inflammasome Activation and Immune Senescence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2016.01.044"}], "href": "https://doi.org/10.1016/j.celrep.2016.01.044"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26876170"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26876170"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Allan Geliebter, Marci E Gluck, Sami A Hashim "}, {"type": "b", "children": [{"type": "t", "text": "Plasma ghrelin concentrations are lower in binge-eating disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Nutr (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jn/135.5.1326"}], "href": "https://doi.org/10.1093/jn/135.5.1326"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15867334"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15867334"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Graham Dominick, Darlene E Berryman, Edward O List, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of mTOR activity in Snell dwarf and GH receptor gene-disrupted mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2014-1690"}], "href": "https://doi.org/10.1210/en.2014-1690"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25456069"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25456069"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Johanna L Barclay, Linda M Kerr, Leela Arthur, et al. "}, {"type": "b", "children": [{"type": "t", "text": "In vivo targeting of the growth hormone receptor (GHR) Box1 sequence demonstrates that the GHR does not signal exclusively through JAK2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2009-0233"}], "href": "https://doi.org/10.1210/me.2009-0233"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19884384"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19884384"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Riia K Junnila, Silvana Duran-Ortiz, Ozan Suer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disruption of the GH Receptor Gene in Adult Mice Increases Maximal Lifespan in Females."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2016-1649"}], "href": "https://doi.org/10.1210/en.2016-1649"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27732088"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27732088"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Archana Vijayakumar, YingJie Wu, Hui Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeted loss of GHR signaling in mouse skeletal muscle protects against high-fat diet-induced metabolic deterioration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db11-0814"}], "href": "https://doi.org/10.2337/db11-0814"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22187377"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22187377"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Jon W Cowan, Xiangdong Wang, Ran Guan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Growth hormone receptor is a target for presenilin-dependent gamma-secretase cleavage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M500621200"}], "href": "https://doi.org/10.1074/jbc.M500621200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15743767"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15743767"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Denise Zaczek, James Hammond, Lii Suen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impact of growth hormone resistance on female reproductive function: new insights from growth hormone receptor knockout mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Reprod (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1095/biolreprod67.4.1115"}], "href": "https://doi.org/10.1095/biolreprod67.4.1115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12297526"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12297526"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Ning Yang, Yao Huang, Jing Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Caveolar and lipid raft localization of the growth hormone receptor and its signaling elements: impact on growth hormone signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M400625200"}], "href": "https://doi.org/10.1074/jbc.M400625200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15010456"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15010456"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Chunxia Lu, P Anil Kumar, Jinhong Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeted deletion of growth hormone (GH) receptor in macrophage reveals novel osteopontin-mediated effects of GH on glucose homeostasis and insulin sensitivity in diet-induced obesity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.460212"}], "href": "https://doi.org/10.1074/jbc.M113.460212"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23595986"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23595986"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Amal Zerrad-Saadi, Martine Lambert-Blot, Claudia Mitchell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GH receptor plays a major role in liver regeneration through the control of EGFR and ERK1/2 activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2010-1193"}], "href": "https://doi.org/10.1210/en.2010-1193"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21540290"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21540290"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Graham Dominick, Jacqueline Bowman, Xinna Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "mTOR regulates the expression of DNA damage response enzymes in long-lived Snell dwarf, GHRKO, and PAPPA-KO mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging Cell (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/acel.12525"}], "href": "https://doi.org/10.1111/acel.12525"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27618784"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27618784"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Edward O List, Darlene E Berryman, Yuji Ikeno, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Removal of growth hormone receptor (GHR) in muscle of male mice replicates some of the health benefits seen in global GHR-/- mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.100766"}], "href": "https://doi.org/10.18632/aging.100766"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26233957"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26233957"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Oge Arum, Michael S Bonkowski, Juliana S Rocha, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The growth hormone receptor gene-disrupted mouse fails to respond to an intermittent fasting diet."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1474-9726.2009.00520.x"}], "href": "https://doi.org/10.1111/j.1474-9726.2009.00520.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19747233"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19747233"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Edward O List, Darlene E Berryman, Mathew Buchman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adipocyte-Specific GH Receptor-Null (AdGHRKO) Mice Have Enhanced Insulin Sensitivity With Reduced Liver Triglycerides."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2018-00850"}], "href": "https://doi.org/10.1210/en.2018-00850"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30462209"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30462209"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Ilona Zawada, Michal M Masternak, Edward O List, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gene expression of key regulators of mitochondrial biogenesis is sex dependent in mice with growth hormone receptor deletion in liver."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.100733"}], "href": "https://doi.org/10.18632/aging.100733"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25855408"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25855408"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Xiangdong Wang, Jing Jiang, Jason Warram, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endotoxin-induced proteolytic reduction in hepatic growth hormone (GH) receptor: a novel mechanism for GH insensitivity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2007-0561"}], "href": "https://doi.org/10.1210/me.2007-0561"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18323468"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18323468"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "P M Gowri, J H Yu, A Shaufl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Recruitment of a repressosome complex at the growth hormone receptor promoter and its potential role in diabetic nephropathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.23.3.815-825.2003"}], "href": "https://doi.org/10.1128/MCB.23.3.815-825.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12529387"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12529387"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Fanxin Ma, Zhe Wei, Chunwei Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Signaling cross talk between growth hormone (GH) and insulin-like growth factor-I (IGF-I) in pancreatic islet β-cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2011-1052"}], "href": "https://doi.org/10.1210/me.2011-1052"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22034225"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22034225"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Patricia Stiedl, Robert McMahon, Leander Blaas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Growth hormone resistance exacerbates cholestasis-induced murine liver fibrosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatology (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hep.27408"}], "href": "https://doi.org/10.1002/hep.27408"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25179284"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25179284"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Katie Robertson, John J Kopchick, Jun-Li Liu "}, {"type": "b", "children": [{"type": "t", "text": "Growth hormone receptor gene deficiency causes delayed insulin responsiveness in skeletal muscles without affecting compensatory islet cell overgrowth in obese mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Endocrinol Metab (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpendo.00378.2005"}], "href": "https://doi.org/10.1152/ajpendo.00378.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16621895"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16621895"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Yingjie Wu, Hui Sun, Jelena Basta-Pljakic, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Deletion of growth hormone receptors in postnatal skeletal muscle of male mice does not alter muscle mass and response to pathological injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2013-1209"}], "href": "https://doi.org/10.1210/en.2013-1209"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23861377"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23861377"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Michael B Stout, William R Swindell, Xu Zhi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptome profiling reveals divergent expression shifts in brown and white adipose tissue from long-lived GHRKO mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.5760"}], "href": "https://doi.org/10.18632/oncotarget.5760"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26436954"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26436954"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Hayden-William Courtland, Hui Sun, Mordechay Beth-On, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Growth hormone mediates pubertal skeletal development independent of hepatic IGF-1 production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Bone Miner Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jbmr.265"}], "href": "https://doi.org/10.1002/jbmr.265"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20928887"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20928887"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Adam Jara, Xingbo Liu, Don Sim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cardiac-Specific Disruption of GH Receptor Alters Glucose Homeostasis While Maintaining Normal Cardiac Performance in Adult Male Mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2015-1686"}], "href": "https://doi.org/10.1210/en.2015-1686"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27035649"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27035649"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Archana Vijayakumar, YingJie Wu, Nicholas J Buffin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Skeletal muscle growth hormone receptor signaling regulates basal, but not fasting-induced, lipid oxidation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0044777"}], "href": "https://doi.org/10.1371/journal.pone.0044777"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23024761"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23024761"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Zhongbo Liu, Oran D Kennedy, Luis Cardoso, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DMP-1-mediated Ghr gene recombination compromises skeletal development and impairs skeletal response to intermittent PTH."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.15-275859"}], "href": "https://doi.org/10.1096/fj.15-275859"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26481310"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26481310"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "Yash Chhabra, Caroline N Nelson, Monika Plescher, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of growth hormone-mediated signal transducer and activator of transcription 5 (STAT5) signaling in mice results in insulin sensitivity with obesity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.201802328R"}], "href": "https://doi.org/10.1096/fj.201802328R"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30779881"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30779881"}]}, {"type": "r", "ref": 44, "children": [{"type": "t", "text": "Xinna Li, Andrzej Bartke, Darlene E Berryman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Direct and indirect effects of growth hormone receptor ablation on liver expression of xenobiotic metabolizing genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Endocrinol Metab (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpendo.00304.2013"}], "href": "https://doi.org/10.1152/ajpendo.00304.2013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23941873"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23941873"}]}, {"type": "r", "ref": 45, "children": [{"type": "t", "text": "Frederick Wasinski, Franco Barrile, João A B Pedroso, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ghrelin-induced Food Intake, but not GH Secretion, Requires the Expression of the GH Receptor in the Brain of Male Mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/endocr/bqab097"}], "href": "https://doi.org/10.1210/endocr/bqab097"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33972988"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33972988"}]}, {"type": "r", "ref": 46, "children": [{"type": "t", "text": "Manabu Nukaya, Yoshiki Takahashi, Frank J Gonzalez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Aryl hydrocarbon receptor-mediated suppression of GH receptor and Janus kinase 2 expression in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S0014-5793(03)01528-X"}], "href": "https://doi.org/10.1016/S0014-5793(03"}, {"type": "t", "text": "01528-X) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14759523"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14759523"}]}, {"type": "r", "ref": 47, "children": [{"type": "t", "text": "Andre Sarmento-Cabral, Mercedes Del Rio-Moreno, Mari C Vazquez-Borrego, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GH directly inhibits steatosis and liver injury in a sex-dependent and IGF1-independent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Endocrinol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1530/JOE-20-0326"}], "href": "https://doi.org/10.1530/JOE-20-0326"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33112796"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33112796"}]}, {"type": "r", "ref": 48, "children": [{"type": "t", "text": "Ryota Masuzaki, Sophia Zhao, M Todd Valerius, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SOCS2 Balances Metabolic and Restorative Requirements during Liver Regeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M115.703264"}], "href": "https://doi.org/10.1074/jbc.M115.703264"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26703468"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26703468"}]}, {"type": "r", "ref": 49, "children": [{"type": "t", "text": "Magdalena Sedek, Lieke M van der Velden, Ger J Strous "}, {"type": "b", "children": [{"type": "t", "text": "Multimeric growth hormone receptor complexes serve as signaling platforms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.523373"}], "href": "https://doi.org/10.1074/jbc.M113.523373"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24280222"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24280222"}]}, {"type": "r", "ref": 50, "children": [{"type": "t", "text": "Adam Gesing, Andrzej Bartke, Feiya Wang, et al. 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