Metabolic effects of growth hormone

Human growth hormone (hGH) is a key ‘player’ in the regulation of growth and metabolism. Several disease conditions, mostly involving growth retardation or GH deficiency, have been approved for recombinant hGH replacement therapy. The focus of this review centers on the metabolic effects of GH on carbohydrates, lipids and proteins. Current knowledge of GH signaling pathways and metabolic attributes of GH deficient and GH excess (acromegaly) states are described. Mouse models commonly used for the study of GH action also are compared to further illustrate the metabolic role of GH. Finally, the metabolic effects of a GH receptor antagonist (Pegvisomant) used for the treatment of acromegaly are mentioned.

[1]  K. Iida,et al.  Growth hormone regulation of p85alpha expression and phosphoinositide 3-kinase activity in adipose tissue: mechanism for growth hormone-mediated insulin resistance. , 2007, Diabetes.

[2]  M. Galderisi,et al.  Treatment with growth hormone receptor antagonist in acromegaly: effect on cardiac structure and performance. , 2007, The Journal of clinical endocrinology and metabolism.

[3]  I. Olkin,et al.  Systematic Review: The Safety and Efficacy of Growth Hormone in the Healthy Elderly , 2007, Annals of Internal Medicine.

[4]  L. Gormsen,et al.  Skeletal Muscle as a Metabolic Target for Growth Hormone , 2007, Hormone Research in Paediatrics.

[5]  J. Kopchick,et al.  Effects of Growth Hormone and Insulin-Like Growth Factor I on Muscle in Mouse Models of Human Growth Disorders , 2007, Hormone Research in Paediatrics.

[6]  Michael K. Skinner,et al.  CHAPTER 38 – Puberty in the Rat , 2006 .

[7]  M. Tena-Sempere.  KiSS-1 and Reproduction: Focus on Its Role in the Metabolic Regulation of Fertility , 2006, Neuroendocrinology.

[8]  J. Kopchick,et al.  Growth Hormone Receptor Antagonists , 2006, Neuroendocrinology.

[9]  A. Herbison,et al.  Postnatal development of kisspeptin neurons in mouse hypothalamus; sexual dimorphism and projections to gonadotropin-releasing hormone neurons. , 2006, Endocrinology.

[10]  M. Tena-Sempere,et al.  Expression of Hypothalamic KiSS-1 System and Rescue of Defective Gonadotropic Responses by Kisspeptin in Streptozotocin-Induced Diabetic Male Rats , 2006, Diabetes.

[11]  M. Tena-Sempere.  GPR54 and kisspeptin in reproduction. , 2006, Human reproduction update.

[12]  M. Tena-Sempere,et al.  Novel signals for the integration of energy balance and reproduction , 2006, Molecular and Cellular Endocrinology.

[13]  M. C. Savanelli,et al.  Beginning to end: cardiovascular implications of growth hormone (GH) deficiency and GH therapy. , 2006, Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society.

[14]  R. Steiner,et al.  Kiss1 Neurons in the Forebrain as Central Processors for Generating the Preovulatory Luteinizing Hormone Surge , 2006, The Journal of Neuroscience.

[15]  S. Ojeda,et al.  Minireview: the neuroendocrine regulation of puberty: is the time ripe for a systems biology approach? , 2006, Endocrinology.

[16]  M. D. De Martino,et al.  Efficacy of 12-month treatment with the GH receptor antagonist pegvisomant in patients with acromegaly resistant to long-term, high-dose somatostatin analog treatment: effect on IGF-I levels, tumor mass, hypertension and glucose tolerance. , 2006, European journal of endocrinology.

[17]  N. Mauras.  Growth Hormone and Testosterone: Effects on Whole Body Metabolism and Skeletal Muscle in Adolescence , 2006, Hormone Research in Paediatrics.

[18]  R. Steiner,et al.  Behavioral / Systems / Cognitive Activation of Gonadotropin-Releasing Hormone Neurons by Kisspeptin as a Neuroendocrine Switch for the Onset of Puberty , 2005 .

[19]  C. Kahn,et al.  Increased P85α Is a Potent Negative Regulator of Skeletal Muscle Insulin Signaling and Induces in Vivo Insulin Resistance Associated with Growth Hormone Excess* , 2005, Journal of Biological Chemistry.

[20]  N. Møller,et al.  Effects of GH replacement therapy in adults on serum levels of leptin and ghrelin: the role of lipolysis. , 2005, European journal of endocrinology.

[21]  R. Steiner,et al.  Regulation of Kiss1 gene expression in the brain of the female mouse. , 2005, Endocrinology.

[22]  M. Tena-Sempere.  Hypothalamic KiSS-1: the missing link in gonadotropin feedback control? , 2005, Endocrinology.

[23]  F. Casanueva,et al.  Changes in hypothalamic KiSS-1 system and restoration of pubertal activation of the reproductive axis by kisspeptin in undernutrition. , 2005, Endocrinology.

[24]  Michael W Parker,et al.  Model for growth hormone receptor activation based on subunit rotation within a receptor dimer , 2005, Nature Structural &Molecular Biology.

[25]  C. Ling,et al.  Prolactin and growth hormone regulate adiponectin secretion and receptor expression in adipose tissue. , 2005, Biochemical and biophysical research communications.

[26]  S. Ojeda,et al.  Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[27]  D. Clemmons.  Role of Insulin-Like Growth Factor Iin Maintaining Normal Glucose Homeostasis , 2005, Hormone Research in Paediatrics.

[28]  M. Salvatore,et al.  The severity of growth hormone deficiency correlates with the severity of cardiac impairment in 100 adult patients with hypopituitarism: an observational, case-control study. , 2004, The Journal of clinical endocrinology and metabolism.

[29]  C. Ronchi,et al.  New therapeutic options for acromegaly. , 2004, Minerva endocrinologica.

[30]  F. Gaytán,et al.  Advanced vaginal opening and precocious activation of the reproductive axis by KiSS‐1 peptide, the endogenous ligand of GPR54 , 2004, The Journal of physiology.

[31]  M. Grumbach,et al.  The Neuroendocrinology of Human Puberty Revisited , 2004, Hormone Research in Paediatrics.

[32]  J. Sánchez-Criado,et al.  Developmental and hormonally regulated messenger ribonucleic acid expression of KiSS-1 and its putative receptor, GPR54, in rat hypothalamus and potent luteinizing hormone-releasing activity of KiSS-1 peptide. , 2004, Endocrinology.

[33]  N. Møller,et al.  Growth Hormone and Glucose Homeostasis , 2004, Hormone Research in Paediatrics.

[34]  M. Lipsett,et al.  Disruption of growth hormone receptor gene causes diminished pancreatic islet size and increased insulin sensitivity in mice. , 2004, American journal of physiology. Endocrinology and metabolism.

[35]  K. Behar,et al.  Comparing adiposity profiles in three mouse models with altered GH signaling. , 2004, Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society.

[36]  H. Matsumoto,et al.  Peripheral administration of metastin induces marked gonadotropin release and ovulation in the rat. , 2004, Biochemical and biophysical research communications.

[37]  V. Quaranta,et al.  Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts , 2004, Journal of Cell Science.

[38]  K. Ellis,et al.  Short- and long-term effects of growth hormone (GH) replacement on protein metabolism in GH-deficient adults. , 2003, The Journal of clinical endocrinology and metabolism.

[39]  S. O’Rahilly,et al.  The GPR54 Gene as a Regulator of Puberty , 2003 .

[40]  J. Toppari,et al.  The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, and changes after migration. , 2003, Endocrine reviews.

[41]  D. Flint,et al.  Effects of Growth Hormone and Prolactin on Adipose Tissue Development and Function , 2003, Pituitary.

[42]  Amy N Holland,et al.  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. , 2003, Endocrinology.

[43]  P. Scherer,et al.  Printed in U.S.A. Copyright © 2003 by The Endocrine Society doi: 10.1210/en.2003-0580 Minireview: The Adipocyte—At the Crossroads of Energy Homeostasis, Inflammation, and Atherosclerosis , 2022 .

[44]  E. Génin,et al.  Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54 , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[45]  P. Trainer.  Metabolic effects of GH antagonism in patients with acromegaly. , 2003, Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society.

[46]  E. Laurila,et al.  Growth hormone replacement therapy induces insulin resistance by activating the glucose-fatty acid cycle. , 2003, The Journal of clinical endocrinology and metabolism.

[47]  J. Kopchick.  Discovery and mechanism of action of pegvisomant. , 2003, European journal of endocrinology.

[48]  H. Matsumoto,et al.  Dramatic elevation of plasma metastin concentrations in human pregnancy: metastin as a novel placenta-derived hormone in humans. , 2003, The Journal of clinical endocrinology and metabolism.

[49]  S. Ojeda,et al.  Glia-to-neuron signaling and the neuroendocrine control of female puberty , 2003, Annals of medicine.

[50]  D. Clemmons,et al.  Growth hormone receptor antagonist improves insulin resistance in acromegaly. , 2002, Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society.

[51]  J. Kopchick,et al.  Growth hormone receptor antagonists. , 2002, Minerva endocrinologica.

[52]  E. C. Stevens,et al.  Growth hormone receptor antagonists: discovery, development, and use in patients with acromegaly. , 2002, Endocrine reviews.

[53]  N. Møller,et al.  Effects of GH on protein metabolism during dietary restriction in man. , 2002, Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society.

[54]  Philippe Froguel,et al.  Disruption of Adiponectin Causes Insulin Resistance and Neointimal Formation* , 2002, The Journal of Biological Chemistry.

[55]  N. Møller,et al.  Pharmacological antilipolysis restores insulin sensitivity during growth hormone exposure. , 2001, Diabetes.

[56]  T. A. Richter,et al.  Neural mechanisms underlying the pubertal increase in LHRH release in the rhesus monkey , 2001, Trends in Endocrinology & Metabolism.

[57]  S. Schiffmann,et al.  The Metastasis Suppressor Gene KiSS-1 Encodes Kisspeptins, the Natural Ligands of the Orphan G Protein-coupled Receptor GPR54* , 2001, The Journal of Biological Chemistry.

[58]  P. Emson,et al.  AXOR12, a Novel Human G Protein-coupled Receptor, Activated by the Peptide KiSS-1* , 2001, The Journal of Biological Chemistry.

[59]  Y. Terauchi,et al.  The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity , 2001, Nature Medicine.

[60]  O. Nishimura,et al.  Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor , 2001, Nature.

[61]  J. Kopchick,et al.  Growth hormone receptor/binding protein (GHR/BP) knockout mice: a 3-year update. , 2001, Molecular genetics and metabolism.

[62]  J. Kopchick,et al.  Biological effects of growth hormone and its antagonist. , 2001, Trends in molecular medicine.

[63]  P. Lobie,et al.  The mechanism of effect of growth hormone on preadipocyte and adipocyte function , 2000, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[64]  P. Carroll,et al.  Growth Hormone Replacement in Adults with Growth Hormone Deficiency: Assessment of Current Knowledge , 2000, Trends in Endocrinology & Metabolism.

[65]  M. S. Tewart,et al.  Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. , 2000 .

[66]  C. Ohlsson,et al.  GH and bone--experimental and clinical studies. , 2000, Endocrine journal.

[67]  F. Casanueva,et al.  Neuroendocrine Regulation and Actions of Leptin , 1999, Frontiers in Neuroendocrinology.

[68]  E. Ghigo,et al.  The growth hormone (GH) response to the arginine plus GH-releasing hormone test is correlated to the severity of lipid profile abnormalities in adult patients with GH deficiency. , 1999, The Journal of clinical endocrinology and metabolism.

[69]  J. Veldhuis,et al.  Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. , 1998, Endocrine reviews.

[70]  M. Wabitsch,et al.  Mitogenic and Antiadipogenic Properties of Human Growth Hormone in Differentiating Human Adipocyte Precursor Cells in Primary Culture1 , 1996, Pediatric Research.

[71]  M. Wabitsch,et al.  The role of growth hormone/insulin-like growth factors in adipocyte differentiation. , 1995, Metabolism: clinical and experimental.

[72]  T. Wagner,et al.  Amino acid residues in the third alpha-helix of growth hormone involved in growth promoting activity. , 1995, Molecular endocrinology.

[73]  J. Flier,et al.  The adipocyte: Storage depot or node on the energy information superhighway? , 1995, Cell.

[74]  C. Wells,et al.  Signal Transduction by the Growth Hormone Receptor , 1994, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[75]  T. Wagner,et al.  In vitro and in vivo studies of antagonistic effects of human growth hormone analogs. , 1994, The Journal of biological chemistry.

[76]  D. Flint,et al.  Influence of growth hormone deficiency on growth and body composition in rats: site-specific effects upon adipose tissue development. , 1993, The Journal of endocrinology.

[77]  L. Lönn,et al.  Treatment of adults with growth hormone (GH) deficiency with recombinant human GH. , 1993, The Journal of clinical endocrinology and metabolism.

[78]  I. Bosaeus,et al.  Increased body fat mass and decreased extracellular fluid volume in adults with growth hormone deficiency , 1993, Clinical endocrinology.

[79]  L. Sjöström,et al.  Effects of growth hormone on fat mass and fat distribution. , 1992, Acta paediatrica (Oslo, Norway : 1992). Supplement.

[80]  M. Ultsch,et al.  Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. , 1992, Science.

[81]  T. Wagner,et al.  Functional antagonism between endogenous mouse growth hormone (GH) and a GH analog results in dwarf transgenic mice. , 1991, Endocrinology.

[82]  U. Smith,et al.  Characterization of the insulin-antagonistic effect of growth hormone in man , 1991, Diabetologia.

[83]  M. Foss,et al.  Peripheral glucose metabolism in acromegaly. , 1991, The Journal of clinical endocrinology and metabolism.

[84]  N. Møller,et al.  Effects of growth hormone on fuel utilization and muscle glycogen synthase activity in normal humans. , 1991, The American journal of physiology.

[85]  T. Wagner,et al.  Expression of a mutated bovine growth hormone gene suppresses growth of transgenic mice. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[86]  P. Roupas,et al.  Isolated adipocytes from growth hormone-treated obese (ob/ob) mice exhibit insulin resistance. , 1990, Biochimica et biophysica acta.

[87]  P. Sönksen,et al.  The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. , 1989, The New England journal of medicine.

[88]  K. Alberti,et al.  Effects of growth hormone on insulin sensitivity and forearm metabolism in normal man , 1989, Diabetologia.

[89]  M. Davidson.  Effect of growth hormone on carbohydrate and lipid metabolism. , 1987, Endocrine reviews.

[90]  M. Haymond,et al.  Changes in leucine kinetics during meal absorption: effects of dietary leucine availability. , 1986, The American journal of physiology.

[91]  B. Beaufrère,et al.  Insulin resistance in acromegaly: defects in both hepatic and extrahepatic insulin action. , 1986, The American journal of physiology.

[92]  H. Green,et al.  A dual effector theory of growth-hormone action. , 1985, Differentiation; research in biological diversity.

[93]  R. DeFronzo,et al.  The effect of growth hormone on glucose metabolism and insulin secretion in man. , 1982, The Journal of clinical endocrinology and metabolism.

[94]  L. Mandarino,et al.  Effects of Growth Hormone on Insulin Action in Man: Mechanisms of Insulin Resistance, Impaired Suppression of Glucose Production, and Impaired Stimulation of Glucose Utilization , 1982, Diabetes.

[95]  E. Newsholme,et al.  The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. , 1963, Lancet.

[96]  B. Houssay.  The Hypophysis and Metabolism , 1936 .

[97]  A. Lely,et al.  Pharmacological Therapy for Acromegaly , 2012, Drugs.

[98]  O. Gavrilova,et al.  Studies involving the GH-IGF axis: Lessons from IGF-I and IGF-I receptor gene targeting mouse models. , 2005, Journal of endocrinological investigation.

[99]  D. Clemmons.  Roles of Insulin-like Growth Factor-I and Growth Hormone in Mediating Insulin Resistance in Acromegaly , 2004, Pituitary.

[100]  M. Bouxsein,et al.  Inhibition of growth hormone action improves insulin sensitivity in liver IGF-1-deficient mice. , 2004, The Journal of clinical investigation.

[101]  H. Gharib,et al.  American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in adults and children--2003 update. , 2003, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[102]  J. Kopchick,et al.  Transgenic models of growth hormone action. , 1999, Annual review of nutrition.

[103]  B. Richelsen.  Action of growth hormone in adipose tissue. , 1997, Hormone research.

[104]  K. Zierler,et al.  EFFECT OF HUMAN GROWTH HORMONE ON MUSCLE AND ADIPOSE TISSUE METABOLISM IN THE FOREARM OF MAN. , 1965, The Journal of clinical investigation.