Abstract
Children with GH deficiency have enlarged fat cells but a reduced number of fat cells compared with healthy children. After treatment with human GH (hGH) both fat cell volume and number are shifted toward normal. To clarify the role of hGH in fat cell formation in human adipose tissue, we investigated the effect of hGH on the proliferation and the differentiation of cultured human adipocyte precursor cells obtained from five children and 10 adults. In a chemically defined serum-free medium treatment of adipocyte precursor cells with hGH led to an increase in IGF-I production and a stimulation of cell proliferation, which could be blocked by a MAb raised against human IGF-I. hGH dose-dependently reduced the number of differentiating cells and suppressed the expression of glycerol-3-phosphate dehydrogenase (GPDH), a marker of adipose differentiation. No significant differences in the hGH effects on proliferation and differentiation capacities were seen between cultures obtained from children and adults. In newly differentiated adipocytes, hGH inhibited glucose uptake and lipogenesis, and stimulated lipolysis. Scatchard analysis of hGH competition experiments using 125I-labeled hGH yielded a linear plot with an apparent Kd of 1.08 nM and an estimated number of 7000 hGH receptors per cell. These data suggest that hGH is able to enlarge the human adipocyte precursor pool via induction of IGF-I synthesis but exhibits a direct antiadipogenic activity. hGH is also able to reduce fat cell volume by reducing lipogenesis and increasing lipolysis.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- DMEM:
-
Dulbecco's modified essential medium
- GPDH:
-
glucose-3-phosphate dehydrogenase
- HBSS:
-
Hanks' balanced salt solution
- hGH:
-
human GH
- HEPES:
-
N- 2-hydroxyethylpiperaine-N'-2-ethanesulfonic acid
- KRH:
-
modified Krebs-Ringer buffer with HEPES
- TITC:
-
transferrin, insulin, triiodothyronine, and cortisol
References
Bonnet FP, Vanderschueren-Lodeweycks M, Eeckels R, Malvaux P 1974 Subcutaneous adipose tissue and lipids in blood in growth hormone deficiency before and after treatment with human growth hormone. Pediatr Res 8: 800–805
Goodman HM, Schwartz Y, Gorin E 1990 Actions of growth hormone on adipose tissue: possible involvement of autocrine and paracrine factors. Acta Paediatr Scand Suppl 367: 132–136
Wabitsch M, Heinze E 1993 Body fat in GH-deficient children and the effect of treatment. Horm Res 40: 5–9
Wabitsch M, Hauner H, Heinze E, Teller W 1994 In vitro effects of growth hormone in adipose tissue. Acta Paediatr Suppl 406: 48–53
Hauner H, Entenmann G, Wabitsch M, Gaillard D, Ailhaud G, Negrel R, Pfeiffer EF 1989 Promoting effect of glucocorticoids on the differentiation of human adipocyte precursor cells cultured in a chemically defined medium. J Clin Invest 84: 1663–1670
Ailhaud G, Grimaldi P, Negrel R 1992 Cellular and molecular aspects of adipose tissue development. Annu Rev Nutr 12: 207–233
Linde S, Hansen B, Lernmark A 1980 Stable iodinated polypeptide hormones prepared by polyacrylamide gel electrophoresis. Anal Biochem 107: 165–176
Wabitsch M, Ilondo MM, Heinze E, Hauner H, Shymko RM, De Meyts P 1996 Biological effects of human growth hormone on rat adipocyte precursor cells in primary culture. Metabolism 45: 1–10
Smith PJ, Wise LS, Berkowitz R, Wan C, Rubin CS 1988 Insulin-like growth factor-I is an essential regulator of the differentiation of 3T3-L1 adipocytes. J Biol Chem 263: 9402–9408
Kather H, Wieland E 1984 Glycerol: luminometric assay. In: Bergmeyer HU (ed) Metabolites of Carbohydrates. Methods of Enzymatic Analysis, 3rd Ed., Vol. VI. Verlag Chemie, Weinheim, pp 510–517
Bradford MM 1976 A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254
Blum WF, Ranke MB, Bierich JR 1986 Isolation and partial characterization of six somatomedin-like peptides from human plasma Cohn fraction IV. Acta Endocrinol 111: 271–284
Rosenbaum M, Gertner JM, Leibel RL 1989 Effects of systemic growth hormone (GH) administration on regional adipose tissue distribution and metabolism in GH-deficient children. J Clin Endocrinol Metab 69: 1274–1281
Hausman GJ, Martin RJ 1989 The influence of human growth hormone on preadipocyte development in serum-supplemented and serum-free cultures of stromalvascular cells from pig adipose tissue. Domest Anim Endocrinol 6: 331–337
Green H, Morikawa M, Nixon T 1985 A dual effector theory of growth-hormone action. Differentiation 29: 195–198
Entenmann G, Hauner H 1996 Realtionship between replication and differentiation in cultured human adipocyte precursor cells. Am J Physiol 270:C1011–C1016
Ottosson M, Vikman-Adolfsson K, Enerbäck S, Elander A, Björntorp P, Eden S 1995 Growth hormone inhibits lipoprotein lipase activity in human adipose tissue. J Clin Endocrinol Metab 80: 936–941
Harant I, Beauville M, Crampes F, Riviere D, Tauber MT, Tauber JP, Garrigues M 1994 Response of fat cells to growth hormone (GH): effect of long term treatment with recombinant human GH in GH-deficient adults. J Clin Endocrinol Metab 78: 1392–1395
Hirsch J, Batechlor B 1976 Adipose tissue cellularity in human obesity. Clin Endocrinol Metab 5: 299–311
Hauner H, Wabitsch M, Pfeiffer EF 1989 Proliferation and differentiation of adipose tissue derived stromal-vascular cells from children at different ages. In: Bjorntorp, P (ed), Obesity in Europe 88. John Libbey, London, pp 195–200
Peter MA, Winterhalter KH, Böni-Schnetzler M, Froesch RE, Zapf J 1993 Regulation of insulin-like growth factor-I (IGF-I) and IGF-binding proteins by growth hormone in rat white adipose tissue. Endocrinology 133: 2624–2631
Nougues J, Reyne Y, Barenton B, Chery T, Garandel V, Soriano J 1993 Differentiation of adipocyte precursors in a serum-free medium is influenced by glucocorticoids and endogenously produced insulin-like growth factor-I. Int J Obes 17: 159–167
Wolverton CK, Azain MJ, Duffy JY, White ME, Ramsay TG 1992 Influence of somatotropin on lipid metabolism and IGF gene expression in porcine adipose tissue. Am J Physiol 263:E637–E645
Gaskin HR, Kim JW, Wright JT, Rund LA, Hausman GJ 1990 Regulation of insulin-like growth factor-I ribonucleic acid expression polypeptide secretion, and binding protein activity by growth hormone in porcine preadipocyte cultures. Endocrinology 126: 622–630
Gavin JR 1981 Growth hormone receptors in canine and human adipocytes: probes for structural determinants of growth hormone binding and action. Procedings of the 63rd Annual Meeting of the Endocrine Society, Abstr 325, p 164
DiGirolamo M, Eden S, Isaksson O, Smith U 1981 Specific binding of human growth hormone to human adipocytes. Proceedings of the 63rd Annual Meeting of the Endocrine Society, Abstr 76, p 101
Acknowledgements
The authors are grateful to Professor Skakkebaek, Rigshospitalet, Copenhagen, for his kind advice and his support of this study. The authors thank Professor Mühlbauer and his staff of the Department of Plastic Surgery, Munich-Bogenhausen, Germany, and Dr. Erichsen, Charlottenlund, Denmark, for their support in obtaining adipose tissue. The excellent technical assistance of S. Schmid and L. Larsoe is gratefully acknowledged. Finally, we are indebted to Bettina Wabitsch for her expert secretarial assistance.
Author information
Authors and Affiliations
Additional information
Presented in part on the 33rd Annual Meeting of the European Society for Paediatric Endocrinology (ESPE), Maastricht, June 22-24, 1994
Rights and permissions
About this article
Cite this article
Wabitsch, M., Braun, S., Hauner, H. et al. Mitogenic and Antiadipogenic Properties of Human Growth Hormone in Differentiating Human Adipocyte Precursor Cells in Primary Culture. Pediatr Res 40, 450–456 (1996). https://doi.org/10.1203/00006450-199609000-00014
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-199609000-00014
This article is cited by
-
The role of 'adipotropins' and the clinical importance of a potential hypothalamic–pituitary–adipose axis
Nature Clinical Practice Endocrinology & Metabolism (2006)
-
Growth Hormone During Development
Reviews in Endocrine and Metabolic Disorders (2005)
-
Characterization of a human preadipocyte cell strain with high capacity for adipose differentiation
International Journal of Obesity (2001)
-
Expressions of Leptin and Insulin‐Like Growth Factor‐I Are Highly Correlated and Region‐Specific in Adipose Tissue of Growing Rats
Obesity Research (2000)
