Short-Term Effects of Growth Hormone on Lipolysis, Glucose and Amino Acid Metabolism Assessed in Serum and Microdialysate of Healthy Young Men

Abstract

Objective We investigated direct effects of a therapeutic growth hormone dose on lipolysis, glucose and amino acid metabolism.

Methods This crossover microdialysis trial involved six healthy male volunteers receiving single subcutaneous injections of both growth hormone (0.035 mg/kg) and placebo (0.9% sodium chloride). The investigation comprised three test days with standard diet. The first day served for adaptation, the second and third one for determining study data during 9 night hours with or without growth hormone. Abdominal subcutaneous microdialysate and blood were continuously collected and forwarded to a separate room next door where hourly taken samples were centrifuged and frozen until analysed.

Results Growth hormone achieved the peak serum level after 3 h followed by a plateau-like course for the next 6 h. Glycerol in microdialysate started to rise 2 h following growth hormone injection achieving significance compared to placebo after 9 h (P<0.05). Serum glycerol increased 4 h after growth hormone administration achieving significance after 6 h (P<0.05). Glucose and amino acid concentrations showed neither in microdialysate nor in serum significant differences between growth hormone and placebo. Serum values of insulin and C-peptide revealed no significant difference between growth hormone and placebo.

Summary and Conclusion As the result of a high single subcutaneous dose of GH, persistent lipolysis can be shown in continuously collected microdialysate and blood, but no indication for gluconeogenesis or protein anabolism.

Key words

growth hormone - metabolic effects - pharmacokinetics - microdialysis - glycerol

^* Current address: MediClin, MVZ Offenburg, Offenburg, Germany

^† Current address: Laboratory Becker & Colleagues, Bamberg, Germany

^‡ Current address: Hospital Barmherzige Brüder, Clinic St. Hedwig, Regensburg, Germany

^§ Current address: Bonn-Rhein-Sieg University of Applied Sciences, Rheinbach, Germany

Publication History

Received: 24 July 2019
Received: 02 October 2019

Accepted: 14 October 2019

Article published online:
07 November 2019

• References

• 1 Möller N, Jörgensen JOL. Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr Rev 2009; 30: 152-177
• 2 Vijayakumar A, Novosyadiyy R, Wu YJ. et al. Biological effects of growth hormone on carbohydrate and lipid metabolism. Growth Horm IGF Res 2010; 20: 1
• 3 Hartman ML, Faria AC, Vance ML. et al. Temporal structure of in vivo growth hormone secretory events in humans. Am J Physiol 1991; 260: E101-E110
• 4 Spiegel K, Leproult R, Colecchia EF. et al. Adaptation oft he 24-h growth hormone profile to a state of sleep debt. Am J Physiol Regul Integr Comp Physiol 2000; 279: R874-R883
• 5 Gasco V, Caputo M, Lanfranco F. et al. Management of GH treatment in adult GH deficiency. Best Pract Res Clin Endocrinol Metab 2017; 31: 13-24
• 6 Grimberg A, DiVall SA, Polychronakos C. et al. Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: Growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency. Horm Res Paediatr 2016; 86: 363-397
• 7 Blankenstein O, Snajderova M, Blair J. et al. Real-life GH dosing patterns in children with GHD, TS or born SGA: A report from the NordiNet^® International Outcome Study. Eur J Endocrinol 2017; 177: 145-155
• 8 Bergan-Roller HE, Sheridan MA. The growth hormone signaling system: Insights into coordinating the anabolic and catabolic actions of growth hormone. Gen Comp Endocrinol 2018; 258: 119-133
• 9 Gravholt CH, Schmitz O, Simonsen L. et al. Effects of a physiological GH pulse on interstitial glycerol in abdominal and femoral adipose tissue. Am J Physiol 1999; 277: E848-E854
• 10 Inoue Y, Copeland EM, Souba WM. Growth hormone enhances amino acid uptake by the human small intestine. Ann Surg 1994; 219: 715-724
• 11 Bifari F, Nisoli E. Branched-chain amino acids differently modulate catabolic and anabolic states in mammals: A pharmacological point of view. Br J Pharmacol 2017; 174: 1366-1377
• 12 Nie C, He T, Zhang W. et al. Branched chain amino acids: Beyond nutrition metabolism. Int J Mol Sci 2018; 19: 954.
• 13 Han Q, Jin-Kui Y, Chen C. Influence of insulin on growth hormone secretion, level and growth hormone signalling. Acta Physiol Sinica 2017; 69: 541-556
• 14 Hammarlund-Udenaes M. Microdialysis is an important technique in systems pharmacology – a historical and methodological review. AAPS J 2017; 19: 1294-1303
• 15 Krebs A, Clement HW, Zimmerer J. et al. Transfer of topical testosterone to subcutaneous microdialysate, blood and saliva in healthy young men. Exp Clin Endocrinol Diabetes 2018; Aug 8
• 16 Thankamony A, Capalbo D, Jonsson PJ. et al. Predictors of insulin-like growth factor-I responses to growth hormone replacement in young adults with growth hormone deficiency. Horm Res Pediatr 2016; 85: 379-388
• 17 van Bunderen CC, Deijen JB, Drent ML. Effect of low-normal and high-normal IGF-1 levels on memory and wellbeing during growth hormone replacement therapy: A randomized clinical trial in adult growth hormone deficiency. Health Qual Life Outcomes 2018; 16: 135 doi:10.1186/s 12955-018-0963-2
• 18 Grimberg A, DiVall SA, Polychronakos C. et al. on behalf of the Drug and Therapeutics Committee and Ethics Committee of the Pediatric Endocrine Society. Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: Growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency. Horm Res Petiatr 2016; 86: 361-397
• 19 Geffner ME. Growth hormone replacement therapy: Transition from adolescence to adulthood. J Clin Res Ped Endo 2009; 1: 205-208
• 20 Frühbeck D, Mendez-Gimenez L. Fernandez-Formoso et al. Regulation of adipocyte lipolysis. Nutr Res Rev 2014; 27: 63-93
• 21 Young SG, Zechner R. Biochemistry and pathophysiology of intravascular and intracellular lipolysis. Genes Dev 2013; 27: 459-484
• 22 Duncan RE, Ahmadian M, Jaworski K. et al. Regulation of lipolysis in adipocytes. Annu Rev Nutr 2007; 27: 79-101
• 23 Bolsoni-Lopes A, Alonso-Vale MIC. Lipolysis and lipases in white adipose tissue – An update. Arch Endocrinol Metab 2015; 59: 335-342
• 24 Lass A, Zimmermann R, Oberer M. et al. Lipolysis – A highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores. Prog Lipid Res 2011; 50: 14-27
• 25 Carmean CM, Cohen RN, Brady MJ. Systemic regulation of adipose metabolism. Biochim Biophys Acta 2014; 1842: 424-430
• 26 Coppack SW, Chinkes DL, Miles JM. et al. A multicompartmental model of in vivo adipose tissue glycerol kinetics and capillary permeability in lean and obese humans. Diabetes 2005; 54: 1934-1941
• 27 Vijayakumar A, Yakar S, LeRoith D. The indricate role of growth hormone in metabolism. Front Endocrinol 2011; 2: 32
• 28 Dietz J, Schwartz J. Growth hormone alters lipolysis and hormone-sensitive lipase activity in 3T3-F442A adipocytes. Metabolism 1991; 40: 800-806
• 29 Karastergiou K, Bredella MA, Lee M-J. et al. Growth hormone receptor expression in human gluteal versus abdominal subcutaneous adipose tissue: Association with body shape. Obesity (Silver Spring) 2016; 24: 1090-1096
• 30 Berryman DE, Henry B, Hjortebjerg R. et al. Developments in our understanding of the effects of growth hormone on white adipose tissue from mice: Implications to the clinic. Expert Rev Endocrinol Metab 2016; 11: 197-207
• 31 Richelsen B. Effect of growth hormone on adipose tissue and skeletal muscle lipoprotein lipase activity in humans. J Endocrinol Invest 1999; 22: 10-15
• 32 Richelsen B, Pedersen SB, Kristensen K. et al. Regulation of lipoprotein lipase and hormone-sensitive lipase activity and gene expression in adipose and muscle tissue by growth hormone treatment during weight loss in obese patients. Metabolism 2000; 49: 906-911
• 33 Ottosson M, Vikman-Adolfsson K, Enerbäck S. et al. Growth hormone inhibits lipoprotein lipase activity in human adipose tissue. J Clin Endocrinol Metab 1995; 80: 936-941
• 34 Braun JEA, Severson DL. Regulation of the synthesis, processing and translocation of lipoprotein lipase. Biochem J 1992; 287: 337-347
• 35 Wang H, Eckel RH. Lipoprotein lipase: From gene to obesity. Am J Physiol Endocrinol Metab 2009; 297: E271-E288
• 36 Hansen TK, Gravholt CH, Orskov H. et al. Dose dependency of the pharmacokinetics and acute lipolytic actions of growth hormone. J Clin Endocrinol Metab 2002; 87: 4691-4698
• 37 Holt R, Sönksen PH. Growth hormone, IGF-I and insulin and their abuse in sport. Br J Pharmacol 2008; 154: 542-556
• 38 Siebert DM, Rao AL. The use and abuse of human growth hormone in sports. Sports Health 2018; 10: 419-426
• 39 Liu Z, Barrett EJ. Human protein metabolism: its measurement and regulation. Am J Physiol Endocrinol Metab 2002; 283: E1105-E1112
• 40 Copeland KC, Nair KS. Acute growth hormone effects on amino acid and lipid metabolism. J Clin Endocrinol Metab 1994; 78: 1040-1047
• 41 Möller N, Schmitz O, Pörksen N. et al. Dose-response studies on the metabolic effects of a growth hormone pulse in humans. Metabolism. 1992; 41: 172-175