In obesity, growth hormone (GH) secretion is impaired which is considered a consequence rather than a cause of obesity. GH regulates the expression of GH receptor and the synthesis of insulin-like growth factor I (IGF-I) in adipocytes. Although GH hyposecretion in obesity may decrease the generation of IGF-I in each adipocyte, increased amounts of IGF-I and GH-binding protein could be secreted from the excessively enlarged amounts of adipose tissue. This may contribute to the normal/high serum-IGF-I and high GH-binding protein levels in obesity. Hyperinsulinemia and increased GH receptor activity may also affect the GH-IGF-I axis. Favorable effects of GH treatment have been observed in obese children and adults. GH treatment decreases adiposity, reduces triglyceride accumulation by inhibiting lipoprotein lipase and enhances lipolysis both via increased hormone-sensitive lipase activity and via induction of beta adrenoreceptors. GH treatment also has a favorable effect on obesity-associated dyslipidemia, but the effects on insulin sensitivity have been conflicting.

Keywords:
Growth hormone, Insulin-like growth factor I, Growth hormone binding protein, Adipocyte, Obesity
1.
WHO: Prevention and management of the global epidemic of obesity. Report of the WHO consultation on obesity. Geneva, WHO, 1997.
2.
Serdula MK, Ivery D, Coates RJ, Freedman DS, Williamson DF, Byers T: Do obese children become obese adults? A review of the literature. Prev Med 1993;22:167–177.
3.
Stunkard A, Coll M, Lundquist S, Meyers A: Obesity and eating style. Arch Gen Psychiatry 1980;7:1127–1129.
4.
Marin P, Björntorp P: Endocrine-metabolic pattern and adipose tissue distribution. Horm Res 1993;39(suppl 3):81–85.
5.
Reaven GM: Pathophysiology of insulin resistance in human disease. Physiol Rev 1995;75:473–486.
6.
Larsson B, Svardsudd K, Welin L, Wilhelmsen L, Björntorp P, Tibblin G: Abdominal adipose tissue distribution, obesity, and risk of cardiovascular disease and death: 13 year follow up of participants in the study of men born in 1913. BMJ 1984;288:1401–1404.
7.
Iranmanesh A, Lizarralde G, Veldhuis JD: Age and relative adiposity are specific negative determinants of the frequency and amplitude of growth hormone (GH) secretory bursts and the half-life of endogenous GH in healthy men. J Clin Endocrinol Metab 1991;73:1081–1088.
8.
Veldhuis JD, Liem AY, South S, Weltman A, Weltman J, Clemmons DA, Abbott R, Mulligan T, Johnson ML, Pincus S, Straume M, Iranmanesh A: Differential impact of age, sex steroid hormones, and obesity on basal versus pulsatile growth hormone secretion in men as assessed in an ultrasensitive chemiluminescence assay. J Clin Endocrinol Metab 1995;80:3209–3222.
9.
Weltman A, Weltman JY, Hartman ML, Abbott RD, Rogol AD, Evans WS, Veldhuis JD: Relationship between age, percentage body fat, fitness, and 24-hour growth hormone release in healthy young adults: Effects of gender. J Clin Endocrinol Metab 1994;78:543–548.
10.
Andreotti AC, Lanzi R, Manzoni MF, Caumo A, Moreschi A, Pontiroli AE: Acute pharmacologic blockade of lipolysis normalizes nocturnal growth hormone levels and pulsatility in obese subjects. Metabolism 1994;43:1207–1213.
11.
Lee EJ, Nam SY, Kim KR, Lee HC, Cho JH, Nam MS, Song YD, Lim SK, Huh KB: Acipimox potentiates growth hormone (GH) response to GH-releasing hormone with or without pyridostigmine by lowering serum free fatty acid in normal and obese subjects. J Clin Endocrinol Metab 1995;80:2495–2498.
12.
Nam SY, Lee EJ, Kim KR, Lee HC, Nam MS, Cho JH, Huh KB: Long-term administration of acipimox potentiates growth hormone response to growth hormone-releasing hormone by decreasing serum free fatty acid in obesity. Metabolism 1996;45:594–597.
13.
Pontiroli AE, Manzoni MF, Malighetti ME, Lanzi R: Restoration of growth hormone (GH) response to GH-releasing hormone in elderly and obese subjects by acute pharmacological reduction of plasma free fatty acids. J Clin Endocrinol Metab 1996;81:3998–4001.
14.
Williams T, Berelowitz M, Joffe SN, Thorner MO, Rivier J, Vale W, Frohman LA: Impaired growth hormone responses to growth hormone-releasing factor in obesity. A pituitary defect reversed with weight reduction. N Engl J Med 1984;311:1403–1407.
15.
Tanaka K, Inoue S, Numata K, Okazaki H, Nakamura S, Takamura Y: Very-low-calorie diet-induced weight reduction reverses impaired growth hormone secretion response to growth hormone-releasing hormone, arginine, and L-dopa in obesity. Metabolism 1990;39:892–896.
16.
Rasmussen MH, Hvidberg A, Juul A, Main KM, Gotfredsen A, Skakkebaek NE, Hilsted J, Skakkebaek NE: Massive weight loss restores 24-hour growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects. J Clin Endocrinol Metab 1995;80:1407–1415.
17.
Slowinska-Srzednicka J, Zgliczynski W, Makowska A, Jeske W, Brzezinska A, Soszynski P, Zgliczynski S: An abnormality of the growth hormone/insulin-like growth factor-I axis in women with polycystic ovary syndrome due to coexistent obesity. J Clin Endocrinol Metab 1992;74:1432–1435.
18.
Frystyk J, Vestbo E, Skjaerbaek C, Mogensen CE, Orskov H: Free insulin-like growth factors in human obesity. Metabolism 1995;44(suppl 4):37–44.
19.
Radetti G, Bozzola M, Pasquino B, Paganini C, Aglialoro A, Livieri C, Barreca A: Growth hormone bioactivity, insulin-like growth factors (IGFs), and IGF binding proteins in obese children. Metabolism 1998;47:1490–1493.
20.
Argente J, Caballo N, Barrios V, Pozo J, Munoz MT, Chowen JA, Hernandez M: Multiple endocrine abnormalities of the growth hormone and insulin-like growth factor axis in prepubertal children with exogenous obesity: Effect of short- and long-term weight reduction. J Clin Endocrinol Metab 1997;82:2076–2083.
21.
Loche S, Cappa M, Borrelli P, Faedda A, Crino A, Cella SG, Corda R, Muller EE, Pintor C: Reduced growth hormone response to growth hormone-releasing hormone in children with simple obesity: Evidence for somatomedin-C mediated inhibition. Clin Endocrinol (Oxf) 1987;27:145–153.
22.
Van Vliet G, Bosson D, Rummens E, Robyn C, Wolter R: Evidence against growth hormone-releasing factor deficiency in children with idiopathic obesity. Acta Endocrinol Suppl (Copenh) 1986;279:403–410.
23.
Caufriez A, Golstein J, Lebrun P, Herchuelz A, Furlanetto R, Copinschi G: Relations between immunoreactive somatomedin C, insulin and T3 patterns during fasting in obese subjects. Clin Endocrinol (Oxf) 1984;20:65–70.
24.
Nam SY, Lee EJ, Kim KR, Cha BS, Song YD, Lim SK, Lee HC, Huh KB: Effect of obesity on total and free insulin-like growth factor (IGF)-1, and their relationship to IGF-binding protein (BP)-1, IGFBP-2, IGFBP-3, insulin, and growth hormone. Int J Obes Relat Metab Disord 1997;21:355–359.
25.
Dietz WH Jr, Hartung R: Changes in height velocity of obese preadolescents during weight reduction. Am J Dis Child 1985;139:705–707.
26.
Thissen JP, Ketelslegers JM, Underwood LE: Nutritional regulation of the insulin-like growth factors. Endocr Rev 1994;15:80–101.
27.
Underwood LE, Smith EP, Clemmons DR, Maes M, Maiter D, Ketelslegers JM: The production and actions of insulin-like growth factors: Their relationship to nutrition and growth; in Tanner JM (ed): Auxology. London, Smith-Gordon, 1989, pp 235–249.
28.
Smith SR, Edgar PJ, Pozefsky T, Chhetri MK, Prout TE. Growth hormone in adults with protein-calorie malnutrition. J Clin Endocrinol Metab 1974;39:53–62.
29.
Hochberg Z, Hertz P, Colin V, Ish-Shalom S, Yeshurun D, Youdim MB, Amit T: The distal axis of growth hormone (GH) in nutritional disorders: GH-binding protein, insulin-like growth factor-I (IGF-I), and IGF-I receptors in obesity and anorexia nervosa. Metabolism 1992;41:106–112.
30.
Zannolli R, Rebeggiani A, Chiarelli F, Morgese G: Hyperinsulinism as a marker in obese children. Am J Dis Child 1993;147:837–841.
31.
Gavin JR 3rd, Saltman RJ, Tollefsen SE: Growth hormone receptors in isolated rat adipocytes. Endocrinology 1982;10:637–643.
32.
Leung DW, Spencer SA, Cachianes G, Hammonds RG, Collins C, Henzel WJ, Barnard R, Waters MJ, Wood WI: Growth hormone receptor and serum binding protein: Purification, cloning and expression. Nature 1987;330:537–543.
33.
Vikman K, Carlsson B, Billig H, Eden S: Expression and regulation of growth hormone (GH) receptor messenger ribonucleic acid (mRNA) in rat adipose tissue, adipocytes, and adipocyte precursor cells: GH regulation of GH receptor mRNA. Endocrinology 1991;129:1155–1161.
34.
Richelsen B: Action of growth hormone in adipose tissue. Horm Res 1997;48(suppl 5):105–110.
35.
Wabitsch M, Hauner H, Heinze E, Teller WM: The role of growth hormone/insulin-like growth factors in adipocyte differentiation. Metabolism 1995;44(suppl 4):45–49.
36.
Tannenbaum GS, Lapointe M, Gurd W, Finkelstein JA: Mechanisms of impaired growth hormone secretion in genetically obese Zucker rats: Roles of growth hormone-releasing factor and somatostatin. Endocrinology 1990;127:3087–3095.
37.
Ahmad I, Steggles AW, Finkelstein JA: In situ hybridization study of obesity-associated alteration in growth hormone mRNA levels. Int J Obes Relat Metab Disord 1992;16:435–441.
38.
Ahmad I, Finkelstein JA, Downs TR, Frohman LA: Obesity-associated decrease in growth hormone-releasing hormone gene expression: A mechanism for reduced growth hormone mRNA levels in genetically obese Zucker rats. Neuroendocrinology 1993;58:332–337.
39.
Massara F, Ghigo E, Molinatti P, Mazza E, Locatelli V, Muller EE, Camanni F: Potentiation of cholinergic tone by pyridostigmine bromide re-instates and potentiates the growth hormone responsiveness to intermittent administration of growth hormone-releasing factor in man. Acta Endocrinol (Copenh) 1986;113:12–16.
40.
Ghigo E, Mazza E, Imperiale E, Rizzi G, Benso L, Muller EE, Camanni F, Massara F: Enhancement of cholinergic tone by pyridostigmine promotes both basal and growth hormone (GH)-releasing hormone-induced GH secretion in children of short stature. J Clin Endocrinol Metab 1987;65:452–456.
41.
Cordido F, Dieguez C, Casanueva FF: Effect of central cholinergic neurotransmission enhancement by pyridostigmine on the growth hormone secretion elicited by clonidine, arginine, or hypoglycemia in normal and obese subjects. J Clin Endocrinol Metab 1990;70:1361–1370.
42.
Loche S, Pintus S, Cella SG, Boghen M, Vannelli S, Benso L, Muller EE, Corda R, Pintor C: The effect of galanin on baseline and GHRH-induced growth hormone secretion in obese children. Clin Endocrinol (Oxf) 1990;33:187–192.
43.
Loche S, Pintus S, Carta D, Muntoni AC, Congiu G, Civolani P, Pintor C: The effect of atenolol on the growth hormone response to growth hormone-releasing hormone in obese children. Acta Endocrinol (Oxf) 1992;126:124–127.
44.
Ghigo E, Procopio M, Boffano GM, Arvat E, Valente F, Maccario M, Mazza E, Camanni F: Arginine potentiates but does not restore the blunted growth hormone response to growth hormone-releasing hormone in obesity. Metabolism 1992;41:560–563.
45.
Procopio M, Invitti C, Maccario M, Grottoli S, Cavagnini F, Camanni F, Ghigo E: Effect of arginine and pyridostigmine on the GHRH-induced GH rise in obesity and Cushing’s syndrome. Int J Obes Relat Metab Disord 1995;19:108–112.
46.
Casanueva FF, Villanueva L, Dieguez C, Diaz Y, Cabranes JA, Szoke B, Scanlon MF, Schally AV, Fernandez-Cruz A: Free fatty acids block growth hormone (GH) releasing hormone-stimulated GH secretion in man directly at the pituitary. J Clin Endocrinol Metab 1987;65:634–642.
47.
Imaki T, Shibasaki T, Masuda A, Hotta M, Yamauchi N, Demura H, Shizume K, Wakabayashi I, Ling N: The effect of glucose and free fatty acids on growth hormone (GH)-releasing factor-mediated GH secretion in rats. Endocrinology 1986;118:2390–2394.
48.
Cordido F, Fernandez T, Martinez T, Penalva A, Peino R, Casanueva FF, Dieguez C: Effect of acute pharmacological reduction of plasma free fatty acids on growth hormone (GH) releasing hormone-induced GH secretion in obese adults with and without hypopituitarism. J Clin Endocrinol Metab 1998;83:4350–4354.
49.
Cordido F, Peino R, Penalva A, Alvarez CV, Casanueva FF, Dieguez C: Impaired growth hormone secretion in obese subjects is partially reversed by acipimox-mediated plasma free fatty acid depression. J Clin Endocrinol Metab 1996;81:914–918.
50.
Maccario M, Procopio M, Grottoli S, Oleandri SE, Boffano GM, Taliano M, Camanni F, Ghigo E: Effects of acipimox, an antilipolytic drug, on the growth hormone (GH) response to GH-releasing hormone alone or combined with arginine in obesity. Metabolism 1996;45:342–346.
51.
Ferrannini E: Physiological and metabolic consequences of obesity. Metabolism 1995;44(suppl 3):15–17.
52.
Kelijman M, Frohman LA: Enhanced growth hormone (GH) responsiveness to GH-releasing hormone after dietary manipulation in obese and nonobese subjects. J Clin Endocrinol Metab 1988;66:489–494.
53.
Forbes GB, Brown MR, Welle SL, Underwood LE: Hormonal response to overfeeding. Am J Clin Nutr 1989;49:608–611.
54.
Gama R, Teale JD, Marks V: The effect of synthetic very low calorie diets on the GH-IGF-1 axis in obese subjects. Clin Chim Acta 1990;188:31–38.
55.
Soliman AT, Hassan AE, Aref MK, Hintz RL, Rosenfeld RG, Rogol AD: Serum insulin-like growth factors I and II concentrations and growth hormone and insulin responses to arginine infusion in children with protein-energy malnutrition before and after nutritional rehabilitation. Pediatr Res 1986;20:1122–1130.
56.
Johnson TR, Blossey BK, Denko CW, Ilan J: Expression of insulin-like growth factor I in cultured rat hepatocytes: Effects of insulin and growth hormone. Mol Endocrinol 1989;3:580–587.
57.
Boni-Schnetzler M, Schmid C, Meier PJ, Froesch ER: Insulin regulates insulin-like growth factor I mRNA in rat hepatocytes. Am J Physiol 1991;260:E846–E851.
58.
Brismar K, Hall K: Clinical applications of IGFBP-1 and its regulation. Growth Regul 1993;3:98–100.
59.
Clemmons DR: Insulin-like growth factor binding proteins and their role in controlling IGF actions. Cytokine Growth Factor Rev 1997;8:45–62.
60.
Kelley KM, Oh Y, Gargosky SE, Gucev Z, Matsumoto T, Hwa V, Ng L, Simpson DM, Rosenfeld RG: Insulin-like growth factor-binding proteins (IGFBPs) and their regulatory dynamics. Int J Biochem Cell Biol 1996;28:619–637.
61.
Suikkari AM, Koivisto VA, Rutanen EM, Yki-Järvinen H, Karonen SL, Seppälä M: Insulin regulates the serum levels of low molecular weight insulin-like growth factor-binding protein. J Clin Endocrinol Metab 1988;66:266–272.
62.
Conover CA, Lee PD, Kanaley JA, Clarkson JT, Jensen MD: Insulin regulation of insulin-like growth factor binding protein-1 in obese and nonobese humans. J Clin Endocrinol Metab 1992;74:1355–1360.
63.
Morris DV, Falcone T: The relationship between insulin sensitivity and insulin-like growth factor-binding protein-1. Gynecol Endocrinol 1996;10:407–412.
64.
Brismar K, Grill V, Efendic S, Hall K: The insulin-like growth factor binding protein-1 in low and high insulin responders before and during dexamethasone treatment. Metabolism 1991;40:728–732.
65.
Saitoh H, Kamoda T, Nakahara S, Hirano T, Nakamura N: Serum concentrations of insulin, insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-1 and -3 and growth hormone binding protein in obese children: Fasting IGFBP-1 is suppressed in normoinsulinaemic obese children. Clin Endocrinol (Oxf) 1998;48:487–492.
66.
Postel-Vinay MC, Saab C, Gourmelen M: Nutritional status and growth hormone-binding protein. Horm Res 1995;44:177–181.
67.
Rasmussen MH, Ho KK, Kjems L, Hilsted J: Serum growth hormone-binding protein in obesity: Effect of a short-term, very low calorie diet and diet-induced weight loss. J Clin Endocrinol Metab 1996;81:1519–1524.
68.
Roelen CA, Koppeschaar HP, de Vries WR, Snel YE, Doerga ME, Zelissen PM, Thijssen JH, Blankenstein MA: Visceral adipose tissue is associated with circulating high affinity growth hormone-binding protein. J Clin Endocrinol Metab 1997;82:760–764.
69.
Nam SY, Kim KR, Song YD, Lim SK, Lee HC, Huh KB: GH-binding protein in obese men with varying glucose tolerance: Relationship to body fat distribution, insulin secretion and the GH-IGF-I axis. Eur J Endocrinol 1999;140:159–163.
70.
Postel-Vinay MC, Leger J, Sotiropoulos A, Delehaye-Zervas MC, Finidori J, Kelly PA: Regulation of growth hormone-binding protein: Clinical implications. J Pediatr Endocrinol 1993;6:241–244.
71.
Baumann G, Shaw MA, Amburn K: Circulating growth hormone binding proteins. J Endocrinol Invest 1994;17:67–81.
72.
Peter MA, Winterhalter KH, Boni-Schnetzler M, Froesch ER, Zapf J: Regulation of insulin-like growth factor-I (IGF-I) and IGF-binding proteins by growth hormone in rat white adipose tissue. Endocrinology 1993;133:2624–2631.
73.
Vikman K, Isgaard J, Eden S: Growth hormone regulation of insulin-like growth factor-I mRNA in rat adipose tissue and isolated rat adipocytes. J Endocrinol 1991;131:139–145.
74.
Gaskins HR, Kim JW, Wright JT, Rund LA, Hausman GJ: Regulation of insulin-like growth factor-I ribonucleic acid expression, polypeptide secretion, and binding protein activity by growth hormone in porcine preadipocyte cultures. Endocrinology 1990;126:622–630.
75.
D’Ercole AJ, Stiles AD, Underwood LE: Tissue concentrations of somatomedin C: Further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action. Proc Natl Acad Sci USA 1984;81:935–939.
76.
Dastot F, Sobrier ML, Duquesnoy P, Duriez B, Goossens M, Amselem S: Alternatively spliced forms in the cytoplasmic domain of the human growth hormone (GH) receptor regulate its ability to generate a soluble GH-binding protein. Proc Natl Acad Sci USA 1996;93:10723–10728.
77.
Ross RJ, Esposito N, Shen XY, Von Laue S, Chew SL, Dobson PR, Postel-Vinay MC, Finidori J: A short isoform of the human growth hormone receptor functions as a dominant negative inhibitor of the full-length receptor and generates large amounts of binding protein. Mol Endocrinol 1997;11:265–273.
78.
Amit T, Bergman T, Dastot F, Youdim MB, Amselem S, Hochberg Z: A membrane-fixed, truncated isoform of the human growth hormone receptor. J Clin Endocrinol Metab 1997;82:3813–3817.
79.
Shen XY, Holt RI, Miell JP, Justice S, Portmann B, Postel-Vinay MC, Ross RJ: Cirrhotic liver expresses low levels of the full-length and truncated growth hormone receptors. J Clin Endocrinol Metab 1998;83:2532–2538.
80.
Wickelgren RB, Landin KL, Ohlsson C, Carlsson LM: Expression of exon 3-retaining and exon 3-excluding isoforms of the human growth hormone-receptor is regulated in an interindividual, rather than a tissue-specific, manner. J Clin Endocrinol Metabol 1995;80:2154–2157.
81.
LaFranchi S, Hanna CE, Torresani T, Schoenle E, Illig R: Comparison of growth hormone binding and metabolic response in rat adipocytes of epididymal, subcutaneous, and retroperitoneal origin. Acta Endocrinol (Copenh) 1985;110:50–55.
82.
Bengtsson BA, Eden S, Lonn L, Kvist H, Stokland A, Lindstedt G, Bosaeus I, Tolli J, Sjöström L, Isaksson OG: Treatment of adults with growth hormone (GH) deficiency with recombinant human GH. J Clin Endocrinol Metab 1993;76:309–317.
83.
Johannsson G, Marin P, Lonn L, Ottosson M, Stenlof K, Björntorp P, Sjöström L, Bengtsson BA: Growth hormone treatment of abdominally obese men reduces abdominal fat mass, improves glucose and lipoprotein metabolism, and reduces diastolic blood pressure J Clin Endocrinol Metab 1997;82:727–734.
84.
Kim KR, Nam SY, Song YD, Lim SK, Lee HC, Huh KB: Low-dose growth hormone treatment with diet restriction accelerates body fat loss, exerts anabolic effect and improves growth hormone secretory dysfunction in obese adults. Horm Res 1999;51:78–84.
85.
Frick GP, Leonard JL, Goodman HM: Effect of hypophysectomy on growth hormone receptor gene expression in rat tissues. Endocrinology 1990;126:3076–3082.
86.
Kamel A, Margery V, Norstedt G, Thoren M, Lindgren AC, Bronnegard M, Marcus C: Growth hormone (GH) treatment up-regulates GH receptor mRNA levels in adipocytes from patients with GH deficiency and Prader-Willi syndrome. Pediatr Res 1995;38:418–421.
87.
Hochberg Z, Barkey RJ, Even L, Peleg I, Youdim MB, Amit T: The effect of human growth hormone therapy on GH binding protein in GH-deficient children. Acta Endocrinol (Copenh) 1991;125:23–27.
88.
Fontoura M, Mugnier E, Brauner R, Rappaport R, Postel-Vinay MC: Effect of growth hormone on the low level of growth hormone binding protein in idiopathic short stature. Clin Endocrinol (Oxf) 1992;37:249–253.
89.
Morikawa M, Nixon T, Green H: Growth hormone and the adipose conversion of 3T3 cells. Cell 1982;29:783–789.
90.
Nixon T, Green H: Contribution of growth hormone to the adipogenic activity of serum. Endocrinology 1984;114:527–532.
91.
Hauner H, Löffler G: Adipogenic factors in human serum promote the adipose conversion of 3T3-L1 fibroblasts. Int J Obes 1986;10:323–330.
92.
Doglio A, Dani C, Grimaldi P, Ailhaud G: Growth hormone regulation of the expression of differentiation-dependent genes in preadipocyte Ob1771 cells. Biochem J 1986;238:123–129.
93.
Deslex S, Negrel R, Ailhaud G: Development of a chemically defined serum-free medium for differentiation of rat adipose precursor cells. Exp Cell Res 1987;168:15–30.
94.
Vassaux G, Negrel R, Ailhaud G, Gaillard D: Proliferation and differentiation of rat adipose precursor cells in chemically defined medium: Differential action of anti-adipogenic agents. J Cell Physiol 1994;161:249–256.
95.
Tontonoz P, Kim JB, Graves RA, Spiegelman BM: ADD1: A novel helix-loop-helix transcription factor associated with adipocyte determination and differentiation. Mol Cell Biol 1993;13:4753–4759.
96.
Kim JB, Spiegelman BM: ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. Genes Dev 1996;10:1096–1107.
97.
Elbrecht A, Chen Y, Cullinan CA, Hayes N, Leibowitz MD, Moller DE, Berger J: Molecular cloning, expression and characterization of human peroxisome proliferator activated receptors gamma 1 and gamma 2. Biochem Biophys Res Commun 1996;224:431–437.
98.
Tontonoz P, Hu E, Graves RA, Budavari AI, Spiegelman BM: mPPAR gamma 2: Tissue-specific regulator of an adipocyte enhancer. Genes Dev 1994;8:1224–1234.
99.
Zhu Y, Qi C, Korenberg JR, Chen XN, Noya D, Rao MS, Reddy JK: Structural organization of mouse peroxisome proliferator-activated receptor gamma (mPPAR gamma) gene: Alternative promoter use and different splicing yield two mPPAR gamma isoforms. Proc Natl Acad Sci USA 1995;92:7921–7925.
100.
Brun RP, Kim JB, Hu E, Altiok S, Spiegelman BM: Adipocyte differentiation: A transcriptional regulatory cascade. Curr Opin Cell Biol 1996;8:826–832.
101.
Distel RJ, Robinson GS, Spiegelman BM: Fatty acid regulation of gene expression: Transcriptional and post-transcriptional mechanisms. J Biol Chem 1992;267:5937–5941.
102.
Moustaid N, Sakamoto K, Clarke S, Beyer RS, Sul HS: Regulation of fatty acid synthase gene transcription. Sequences that confer a positive insulin effect and differentiation-dependent expression in 3T3-L1 preadipocytes are present in the 332 bp promoter. Biochem J 1993;292:767–772.
103.
Moustaid N, Sul HS: Regulation of expression of the fatty acid synthase gene in 3T3-L1 cells by differentiation and triiodothyronine. J Biol Chem 1991;266:18550–18554.
104.
Hansen LH, Madsen B, Teisner B, Nielsen JH, Billestrup N: Characterization of the inhibitory effect of growth hormone on primary preadipocyte differentiation. Mol Endocrinol 1998;12:1140–1149.
105.
Hu E, Kim JB, Sarraf P, Spiegelman BM: Inhibition of adipogenesis through MAP kinase-mediated phosphorylation of PPARgamma. Science 1996;274:2100–2103.
106.
Hauner H, Rohrig K, Petruschke T: Effects of epidermal growth factor (EGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) on human adipocyte development and function. Eur J Clin Invest 1995;25:90–96.
107.
Smith PJ, Wise LS, Berkowitz R, Wan C, Rubin CS: Insulin-like growth factor-I is an essential regulator of the differentiation of 3T3-L1 adipocytes. J Biol Chem 1988;263:9402–9408.
108.
Schmidt W, Poll-Jordan G, Löffler G: Adipose conversion of 3T3-L1 cells in a serum-free culture system depends on epidermal growth factor, insulin-like growth factor I, corticosterone, and cyclic AMP. J Biol Chem 1990;265:15489–15495.
109.
Bonnet F, Vanderschueren-Lodeweyckx M, Eeckels R, Malvaux P: Subcutaneous adipose tissue and lipids in blood in growth hormone deficiency before and after treatment with human growth hormone. Pediatr Res 1974;8:800–805.
110.
Davidson MB: Effect of growth hormone on carbohydrate and lipid metabolism. Endocr Rev 1987;8:115–131.
111.
Dietz J, Schwartz J: Growth hormone alters lipolysis and hormone-sensitive lipase activity in 3T3-F442A adipocytes. Metabolism 1991;40:800–806.
112.
Adamafio NA, Ng FM: Effects of growth hormone on lipogenesis and glucose oxidation in genetically GH-deficient mice. Mol Cell Endocrinol 1984;37:241–244.
113.
Landron D, Guerre-Millo M, Postel-Vinay MC, Lavau M: Relationship between increased binding and insulin-like effects of human growth hormone in adipocytes from young fa/fa rats. Endocrinology 1989;124:2305–2313.
114.
Marcus C, Bolme P, Micha-Johansson G, Margery V, Bronnegard M: Growth hormone increases the lipolytic sensitivity for catecholamines in adipocytes from healthy adults. Life Sci 1994;54:1335–1341.
115.
Wabitsch M, Hauner H, Heinze E, Teller W: In vitro effects of growth hormone in adipose tissue. Acta Paediatr 1994;406:48–53.
116.
Ridderstrale M, Tornqvist H: Effects of tyrosine kinase inhibitors on tyrosine phosphorylations and the insulin-like effects in response to human growth hormone in isolated rat adipocytes. Endocrinology 1996;137:4650–4656.
117.
Shimizu M, Torti F, Roth RA: Characterization of the insulin and insulin-like growth factor receptors and responsitivity of a fibroblast/adipocyte cell line before and after differentiation. Biochem Biophy Res Commun 1986;137:552–558.
118.
O’Neal DN, Kalfas A, Dunning PL, Christopher MJ, Sawyer SD, Ward GM, Alford FP: The effect of 3 months of recombinant human growth hormone (GH) therapy on insulin and glucose-mediated glucose disposal and insulin secretion in GH-deficient adults: A minimal model analysis. J Clin Endocrinol Metab 1994;79:975–983.
119.
Rizza RA, Mandarino LJ, Gerich JE: Effects of growth hormone on insulin action in man. Mechanisms of insulin resistance, impaired suppression of glucose production, and impaired stimulation of glucose utilization. Diabetes 1982;31:663–669.
120.
Maloff BL, Levine JH, Lockwood DH: Direct effects of growth hormone on insulin action in rat adipose tissue maintained in vitro. Endocrinology 1980;107:538–544.
121.
Schwartz J: Growth hormone directly alters glucose utilization in 3T3 adipocytes. Biochem Biophys Res Commun 1984;125:237–243.
122.
Schwartz J, Carter-Su C: Effects of growth hormone on glucose metabolism and glucose transport in 3T3-F442A cells: Dependence on cell differentiation. Endocrinology 1988;122:2247–2256.
123.
Tai PK, Liao JF, Chen EH, Dietz J, Schwartz J, Carter-Su C: Differential regulation of two glucose transporters by chronic growth hormone treatment of cultured 3T3-F442A adipose cells. J Biol Chem 1990;265:21828–21834.
124.
Kilgour E, Baldwin SA, Flint DJ: Divergent regulation of rat adipocyte GLUT1 and GLUT4 glucose transporters by GH. J Endocrinol 1995;145:27–33.
125.
Smith TR, Elmendorf JS, David TS, Turinsky J: Growth hormone-induced insulin resistance: Role of the insulin receptor, IRS-1, GLUT-1, and GLUT-4. Am J Physiol 1997;272:E1071–E1079.
126.
Brook CG: Effect of human growth hormone treatment on adipose tissue in children. Arch Dis Child 1973;48:725–728.
127.
Beauville M, Harant I, Crampes F, Rivière D, Tauber MT, Tauber JP, Garrigues M: Effect of long-term rhGH administration in GH-deficient adults on fat cell epinephrine response. Am J Physiol 1992;263:E467–E472.
128.
Kamel A, Norgren S, Eliman A, Danielsson P, Marcus C: Effect of growth hormone treatment in obese prepubertal boys. J Clin Endocrinol Metab 2000;85:1412–1419.
129.
Yang S, Xu X, Björntorp P, Eden S: Additive effects of growth hormone and testosterone on lipolysis in adipocytes of hypophysectomized rats. J Endocrinol 1995;147:147–152.
130.
Yang S, Björntorp P, Liu X, Eden S: Growth hormone treatment of hypophysectomized rats increases catecholamine-induced lipolysis and the number of beta-adrenergic receptors in adipocytes: No differences in the effects of growth hormone on different fat depots. Obes Res 1996;4:471–478.
131.
Kamel A, Norgren S, Lindgren AC, Luthman H, Arner P, Marcus C: Effect of growth hormone treatment on insulin action in adipocytes from children with Prader-Willi syndrome. Eur J Endocrinol 1998;138:510–516.
132.
Eckel RH, Yost TJ: Weight reduction increases adipose tissue lipoprotein lipase responsiveness in obese women. J Clin Invest 1987;80:992–997.
133.
Richelsen B, Pedersen SB, Borglum JD, Möller-Pedersen T, Jörgensen J, Jorgensen JO: Growth hormone treatment of obese women for 5 wk: Effect on body composition and adipose tissue LPL activity. Am J Physiol 1994;266:E211–E216.
134.
Ottosson M, Vikman-Adolfsson K, Enerbäck S, Elander A, Björntorp P, Eden S: Growth hormone inhibits lipoprotein lipase activity in human adipose tissue. J Clin Endocrinol Metab 1995;80:936–941.
135.
Rosenbaum M, Gertner JM, Leibel RL: Effects of systemic growth hormone (GH) administration on regional adipose tissue distribution and metabolism in GH-deficient children. J Clin Endocrinol Metab 1989;69:1274–1281.
136.
Flint DJ, Gardner MJ: Influence of growth hormone deficiency on growth and body composition in rats: Site-specific effects upon adipose tissue development. J Endocrinol 1993;137:203–211.
137.
Bengtsson BA: The consequences of growth hormone deficiency in adults. Acta Endocrinol (Copenh) 1993;128(suppl 2):2–5.
138.
Beshyah SA, Johnston DG: Cardiovascular disease and risk factors in adults with hypopituitarism. Clin Endocrinol (Oxf) 1999;50:1–15.
139.
Rosen T, Johannsson G, Johansson JO, Bengtsson BA: Consequences of growth hormone deficiency in adults and the benefits and risks of recombinant human growth hormone treatment. Horm Res 1995;43:93–99.
140.
Bengtsson BA, Johannsson G: Effect of growth hormone therapy on early atherosclerotic changes in GH-deficient adults. Lancet 1999;353:1898–1899.
141.
Johannsson G, Bengtsson BA: Growth hormone and the metabolic syndrome. J Endocrinol Invest 1999;22(5 suppl):41–46.
142.
Forbes GB: Weight loss during fasting: Implications for the obese. Am J Clin Nutr 1970;23:1212–1219.
143.
Snyder DK, Clemmons DR, Underwood LE: Treatment of obese, diet-restricted subjects with growth hormone for 11 weeks: Effects on anabolism, lipolysis, and body composition. J Clin Endocrinol Metab 1988;67:54–61.
144.
Jörgensen JO, Pedersen SB, Borglum J, Möller N, Schmitz O, Christiansen JS, Richelsen B: Fuel metabolism, energy expenditure, and thyroid function in growth hormone-treated obese women: A double-blind placebo-controlled study. Metabolism 1994;43:872–877.
145.
Tagliaferri M, Scacchi M, Pincelli AI, Berselli ME, Silvestri P, Montesano A, Ortolani S, Dubini A, Cavagnini F: Metabolic effects of biosynthetic growth hormone treatment in severely energy-restricted obese women. Int J Obes Relat Metab Disord 1998;22:836–841.
146.
Snyder DK, Underwood LE, Clemmons DR: Persistent lipolytic effect of exogenous growth hormone during caloric restriction. Am J Med 1995;98:129–134.
147.
Snyder DK, Underwood LE, Clemmons DR: Anabolic effects of growth hormone in obese diet-restricted subjects are dose dependent. Am J Clin Nutr 1990;52:431–437.
148.
Clemmons DR, Snyder DK, Williams R, Underwood LE: Growth hormone administration conserves lean body mass during dietary restriction in obese subjects. J Clin Endocrinol Metab 1987;64:878–883.
149.
Cuneo RC, Salomon F, Wilmshurst P, Byrne C, Wiles CM, Hesp R, Sonksen PH: Cardiovascular effects of growth hormone treatment in growth-hormone-deficient adults: Stimulation of the renin-aldosterone system. Clin Sci 1991;81:587–592.
150.
Rudling M, Norstedt G, Olivecrona H, Reihner E, Gustafsson JA, Angelin B: Importance of growth hormone for the induction of hepatic low density lipoprotein receptors. Proc Natl Acad Sci USA 1992;89:6983–6987.
151.
Chong PK, Jung RT, Scrimgeour CM, Rennie MJ, Paterson CR: Energy expenditure and body composition in growth hormone deficient adults on exogenous growth hormone. Clin Endocrinol (Oxf) 1994;40:103–110.
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2000
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