Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Human growth hormone receptor (GHR) expression in obesity: I. GHR mRNA expression in omental and subcutaneous adipose tissues of obese women

Abstract

Objectives:

Growth hormone (GH)-deficient individuals display increased adiposity that can be effectively reduced by GH therapy because of GH's lipolytic effects. However, similar GH treatments of individuals with idiopathic obesity (not associated with an endocrinopathy/syndrome) have had little success. We hypothesized that this form of obesity may be associated with GH resistance at the level of the adipocyte because of reduced GH receptor (GHR) expression.

Subjects and methods:

We studied GHR expression in omental and subcutaneous fat tissues from a cohort of 55 women ranging from lean to obese by various adiposity parameters. mRNA levels of total GHR and the dominant-negative truncated GHR1−279 (trGHR) form were assayed by quantitative reverse transcriptase-PCR. Associations between adiposity measures and GHR levels as well as trGHR/GHR ratios were analyzed.

Results:

Total GHR mRNA expression was 2–3-fold lower in omental as well as subcutaneous adipose tissues of obese compared with lean women (P0.05–0.001). Lean individuals expressed higher GHR mRNA levels in omental fat compared with subcutaneous (P0.01); in obese women, this depot-specific difference was lost. Omental and subcutaneous adipose GHR mRNA levels displayed significant negative correlations with a spectrum of indicators of obesity while, in subcutaneous fat, there was a significantly higher trGHR/GHR ratio with increasing adiposity (P0.05).

Conclusion:

These results support our hypothesis that, with obesity, there is lower GHR expression in the adipocyte, and suggest one possible explanation why GH supplementation is not an effective treatment for individuals with idiopathic obesity.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Bengtsson BA, Brummer RJ, Eden S, Bosaeus I, Lindstedt G . Body composition in acromegaly: the effect of treatment. Clin Endocrinol (Oxf) 1989; 31: 481–490.

    Article  CAS  Google Scholar 

  2. Laron Z, Ginsberg S, Lilos P, Arbiv M, Vaisman N . Body composition in untreated adult patients with Laron syndrome (primary GH insensitivity). Clin Endocrinol (Oxf) 2006; 65: 114–117.

    Article  CAS  Google Scholar 

  3. Hoffman DM, O’Sullivan AJ, Freund J, Ho KK . Adults with growth hormone deficiency have abnormal body composition but normal energy metabolism. J Clin Endocrinol Metab 1995; 80: 72–77.

    CAS  PubMed  Google Scholar 

  4. Ballesteros M, Leung KC, Ross RJ, Iismaa TP, Ho KK . Distribution and abundance of messenger ribonucleic acid for growth hormone receptor isoforms in human tissues. J Clin Endocrinol Metab 2000; 85: 2865–2871.

    CAS  PubMed  Google Scholar 

  5. Jorgensen JOL, Moller L, Krag M, Billestrup N, Christiansen JS . Effects of growth hormone on glucose and fat metabolism in human subjects. Endocrinol Metab Clin North Am 2007; 36: 75–88.

    Article  PubMed  Google Scholar 

  6. Nam SY, Lobie PE . The mechanism of effect of growth hormone on preadipocyte and adipocyte function. Obes Rev 2000; 1: 73–86.

    Article  CAS  PubMed  Google Scholar 

  7. Wei Y, Rhani Z, Goodyer CG . Characterization of growth hormone receptor messenger ribonucleic acid variants in human adipocytes. J Clin Endocrinol Metab 2006; 91: 1901–1908.

    Article  CAS  PubMed  Google Scholar 

  8. Beauregard C, Utz AL, Schaub AE, Nachtigall L, Biller BM, Miller KK et al. Growth hormone decreases visceral fat and improves cardiovascular risk markers in women with hypopituitarism: a randomized, placebo-controlled study. J Clin Endocrinol Metab 2008; 93: 2063–2071.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Boot AM, Engels MA, Boerma GJ, Krenning EP, de Muinck Keizer-Schrama SM . Changes in bone mineral density, body composition, and lipid metabolism during growth hormone (GH) treatment in children with GH deficiency. J Clin Endocrinol Metab 1997; 82: 2423–2428.

    CAS  PubMed  Google Scholar 

  10. Heffernan MA, Thorburn AW, Fam B, Summers R, Conway-Campbell B, Waters MJ et al. Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. Int J Obes Relat Metab Disord 2001; 25: 1442–1449.

    Article  CAS  PubMed  Google Scholar 

  11. Kamel A, Margery V, Norstedt G, Thoren M, Lindgren AC, Bronnegard M et al. 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.

    Article  CAS  PubMed  Google Scholar 

  12. Mekala KC, Tritos NA . Effects of recombinant human growth hormone therapy in obesity in adults: a metaanalysis. J Clin Endocrinol Metab 2009; 94: 130–137.

    Article  CAS  PubMed  Google Scholar 

  13. Goodyer CG, Figueiredo RM, Krackovitch S, De Souza LL, Manalo JA, Zogopoulos G . Characterization of the growth hormone receptor in human dermal fibroblasts and liver during development. Am J Physiol Endocrinol Metab 2001; 281: E1213–E1220.

    Article  CAS  PubMed  Google Scholar 

  14. Goodyer CG, Zogopoulos G, Schwartzbauer G, Zheng H, Hendy GN, Menon RK . Organization and evolution of the human growth hormone receptor gene 5′-flanking region. Endocrinology 2001; 142: 1923–1934.

    Article  CAS  PubMed  Google Scholar 

  15. Zou L, Menon RK, Sperling MA . Induction of mRNAs for the growth hormone receptor gene during mouse 3T3-L1 preadipocyte differentiation. Metabolism 1997; 46: 114–118.

    Article  CAS  PubMed  Google Scholar 

  16. Ross RJM, Esposito N, Shen XY, Von Laue S, Chew SL, Dobson PRM et al. 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: 265–274.

    Article  CAS  PubMed  Google Scholar 

  17. Drolet R, Richard C, Sniderman AD, Mailloux J, Fortier M, Huot C et al. Hypertrophy and hyperplasia of abdominal adipose tissues in women. Int J Obes (Lond) 2008; 32: 283–291.

    Article  CAS  Google Scholar 

  18. Morisset AS, Huot C, Legare D, Tchernof A . Circulating IL-6 concentrations and abdominal adipocyte isoproterenol-stimulated lipolysis in women. Obesity (Silver Spring) 2008; 16: 1487–1492.

    Article  CAS  Google Scholar 

  19. Blouin K, Nadeau M, Mailloux J, Daris M, Lebel S, Luu-The V et al. Pathways of adipose tissue androgen metabolism in women: depot differences and modulation by adipogenesis. Am J Physiol Endocrinol Metab 2009; 296: E244–E255.

    Article  CAS  PubMed  Google Scholar 

  20. Luu-The V, Paquet N, Calvo E, Cumps J . Improved real-time RT-PCR method for high-throughput measurements using second derivative calculation and double correction. Biotechniques 2005; 38: 287–293.

    Article  CAS  PubMed  Google Scholar 

  21. Blouin K, Blanchette S, Richard C, Dupont P, Luu-The V, Tchernof A . Expression and activity of steroid aldoketoreductases 1C in omental adipose tissue are positive correlates of adiposity in women. Am J Physiol Endocrinol Metab 2005; 288: E398–E404.

    Article  CAS  PubMed  Google Scholar 

  22. LeRoith D, Yakar S . Mechanisms of disease: metabolic effects of growth hormone and insulin-like growth factor 1. Nat Clin Pract Endocrinol Metab 2007; 3: 302–310.

    Article  CAS  PubMed  Google Scholar 

  23. 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.

    CAS  PubMed  Google Scholar 

  24. Roelen CA, Koppeschaar HP, de Vries WR, Snel YE, Doerga ME, Zelissen PM et al. Visceral adipose tissue is associated with circulating high affinity growth hormone-binding protein. J Clin Endocrinol Metab 1997; 82: 760–764.

    Article  CAS  PubMed  Google Scholar 

  25. Bouhours-Nouet N, Gatelais F, Boux de CF, Rouleau S, Coutant R . The insulin-like growth factor-I response to growth hormone is increased in prepubertal children with obesity and tall stature. J Clin Endocrinol Metab 2007; 92: 629–635.

    Article  CAS  PubMed  Google Scholar 

  26. Gleeson HK, Lissett CA, Shalet SM . Insulin-like growth factor-I response to a single bolus of growth hormone is increased in obesity. J Clin Endocrinol Metab 2005; 90: 1061–1067.

    Article  CAS  PubMed  Google Scholar 

  27. Fisker S, Hansen B, Fuglsang J, Kristensen K, Ovesen P, Orskov H et al. Gene expression of the GH receptor in subcutaneous and intraabdominal fat in healthy females: relationship to GH-binding protein. Eur J Endocrinol 2004; 150: 773–777.

    Article  CAS  PubMed  Google Scholar 

  28. Johannsson G, Bjarnason R, Bramnert M, Carlsson LM, Degerblad M, Manhem P et al. The individual responsiveness to growth hormone (GH) treatment in GH-deficient adults is dependent on the level of GH-binding protein, body mass index, age, and gender. J Clin Endocrinol Metab 1996; 81: 1575–1581.

    CAS  PubMed  Google Scholar 

  29. Higami Y, Pugh TD, Page GP, Allison DB, Prolla TA, Weindruch R . Adipose tissue energy metabolism: altered gene expression profile of mice subjected to long-term caloric restriction. FASEB J 2004; 18: 415–417.

    Article  CAS  PubMed  Google Scholar 

  30. Zhang Z, Li Q, Liu F, Sun Y, Zhang J . Prevention of diet-induced obesity by safflower oil: insights at the levels of PPAR{alpha}, Orexin, and Ghrelin ge. Acta Biochim Biophys Sin 2010; 42: 202–209.

    Article  CAS  PubMed  Google Scholar 

  31. Kopchick JJ, Andry JM . Growth hormone (GH), GH receptor, and signal transduction. Mol Genet Metab 2000; 71: 293–314.

    Article  CAS  PubMed  Google Scholar 

  32. Cali AM, Caprio S . Obesity in children and adolescents. J Clin Endocrinol Metab 2008; 93 (Suppl 1): S31–S36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Denson LA, Menon RK, Shaufl A, Bajwa HS, Williams CR, Karpen SJ . TNF-alpha downregulates murine hepatic growth hormone receptor expression by inhibiting Sp1 and Sp3 binding. J Clin Invest 2001; 107: 1451–1458.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Thimmarayappa J, Sun J, Schultz LE, Dejkhamron P, Lu C, Giallongo A et al. Inhibition of growth hormone receptor gene expression by saturated fatty acids: role of Kruppel-like zinc finger factor, ZBP-89. Mol Endocrinol 2006; 20: 2747–2756.

    Article  CAS  PubMed  Google Scholar 

  35. Mauriege P, Despres JP, Prud’homme D, Pouliot MC, Marcotte M, Tremblay A et al. Regional variation in adipose tissue lipolysis in lean and obese men. J Lipid Res 1991; 32: 1625–1633.

    CAS  PubMed  Google Scholar 

  36. Fain JN . Release of inflammatory mediators by human adipose tissue is enhanced in obesity and primarily by the nonfat cells: a review. Mediators Inflamm 2010; 2010: 513948.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Mericq V, Medina P, Bouwman C, Johnson MC, Godoy J, Lopez T et al. Expression and activity of 11beta-hydroxysteroid dehydrogenase type 1 enzyme in subcutaneous and visceral adipose tissue of prepubertal children. Horm Res 2009; 71: 89–93.

    CAS  PubMed  Google Scholar 

  38. Hellmer J, Marcus C, Sonnenfeld T, Arner P . Mechanisms for differences in lipolysis between human subcutaneous and omental fat cells. J Clin Endocrinol Metab 1992; 75: 15–20.

    CAS  PubMed  Google Scholar 

  39. 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.

    Article  CAS  PubMed  Google Scholar 

  40. Harman-Boehm I, Bluher M, Redel H, Sion-Vardy N, Ovadia S, Avinoach E et al. Macrophage infiltration into omental versus subcutaneous fat across different populations: effect of regional adiposity and the comorbidities of obesity. J Clin Endocrinol Metab 2007; 92: 2240–2247.

    Article  CAS  PubMed  Google Scholar 

  41. Cuneo RC, Salomon F, Watts GF, Hesp R, Sonksen PH . Growth hormone treatment improves serum lipids and lipoproteins in adults with growth hormone deficiency. Metabolism 1993; 42: 1519–1523.

    Article  CAS  PubMed  Google Scholar 

  42. Eden S, Wiklund O, Oscarsson J, Rosen T, Bengtsson BA . Growth hormone treatment of growth hormone-deficient adults results in a marked increase in Lp(a) and HDL cholesterol concentrations. Arterioscler Thromb 1993; 13: 296–301.

    Article  CAS  PubMed  Google Scholar 

  43. Garry P, Collins P, Devlin JG . An open 36-month study of lipid changes with growth hormone in adults: lipid changes following replacement of growth hormone in adult acquired growth hormone deficiency. Eur J Endocrinol 1996; 134: 61–66.

    Article  CAS  PubMed  Google Scholar 

  44. Bansch D, Dirkes-Kersting A, Schulte H, Assmann G, von Eckardstein A . Basal growth hormone levels are positively correlated with high-density lipoprotein cholesterol levels in women. Metabolism 1997; 46: 1039–1043.

    Article  CAS  PubMed  Google Scholar 

  45. Bansch D, Chen-Haudenschild C, Dirkes-Kersting A, Schulte H, Assmann G, von EA . Basal growth hormone levels in women are positively correlated with high-density lipoprotein cholesterol and apolipoprotein A-I independently of insulin-like growth factor 1 or insulin. Metabolism 1998; 47: 339–344.

    Article  CAS  PubMed  Google Scholar 

  46. Kenth G, Mergelas J, Goodyer C . Developmental changes in the human growth hormone receptor and its signal transduction pathways. J Endocrinol 2008; 198: 71–82.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by operating funds (CGG) and studentships (AE, AV) from the Canadian Institutes of Health Research. CGG is a member of the McGill University Health Centre Research Institute, which is supported in part by the Fonds de recherches en santé du Québec (FRSQ). AT is the recipient of a senior scholarship from the FRSQ. We would like to thank all the women who participated in this project.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to C G Goodyer.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Erman, A., Veilleux, A., Tchernof, A. et al. Human growth hormone receptor (GHR) expression in obesity: I. GHR mRNA expression in omental and subcutaneous adipose tissues of obese women. Int J Obes 35, 1511–1519 (2011). https://doi.org/10.1038/ijo.2011.23

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2011.23

Keywords

This article is cited by

Search

Quick links