Journal List > J Korean Soc Endocrinol > v.21(3) > 1063859

Jung, Rhee, Kim, Oh, Lee, and Kim: The Relationship of Ghrelin and Leptin with the Biochemical Markers for Adult Growth Hormone Deficiency

Abstract

Background

In spite of the increasing information that has recently been accumulated on the involvement of ghrelin and leptin in energy balance control, the relationship between ghrelin or leptin and the growth hormone (GH)-Insulin like growth factor-1 (IGF-1) axis in the pathological condition characterized by growth hormone deficiency (GHD) has been poorly clarified. Therefore, we performed this study to evaluate the correlation of the plasma levels of ghrelin and leptin with the anthropometric and biochemical markers in GHD adults and also in healthy adults.

Methods

For the 60 male adults (GHD, n = 12; healthy control, n = 48; average age, 54 years), we investigated the correlations between the serum leptin and ghrelin levels with the anthropometric and biochemical factors in the two groups, as divided by their GH status. The diagnosis of GHD was made on the basis of a peak response for serum GH of less than 5 µ/L to a GH provocative test (L-dopa test). All the subjects underwent assessment of waist circumference, BMI and percentage body fat for their body composition. The plasma ghrelin, leptin, insulin, GH and IGF-1 were measured.

Results

The groups were well-matched for their age, BMI, waist circumference and percentage of body fat. The ghrelin and leptin levels were not significantly different between the two groups. There was no correlation between the peak GH level or the area under the curve of growth hormone (GHAUC) and the ghrelin concentrations in the GHD subjects. Plasma leptin correlated positively with the percentage of body fat, the total cholesterol and the LDL-cholesterol, but it had no correlation with the peak GH or GHAUC in the GHD subjects.

Conclusions

It is possible that the ghrelin concentrations appeared normal in the GHD subjects. Further studies are needed to clarify these controversies about the relation of ghrelin and leptin with the GH and IGF-1 levels.

Figures and Tables

Fig. 1
Correlations between the peak GH levels, GHAUC and the log(Ln) leptin in the control group.
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Fig. 2
Correlations between the peak GH levels, GHAUC and the log (Ln) ghrelin in the control group.
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Table 1
Baseline characteristics and the results of the GHD patients and the control subjects
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BMI, body mass index; GHAUC, area under the curve of growth hormone; GHD, growth hormone deficiency; HDL-C, high density lipoprotein cholesterol; IGF-1, insulin-like growth factor-1; LDL-C, low density lipoprotein cholesterol; Peak GH, peak value of growth hormone; WC, waist circumference; WHR, waist-hip ratio.

*P values are for the comparisons of the mean values between the GHD patients and the control subjects by the Mann-Whitney U test.

Table 2
Correlation analysis of leptin and ghrelin with the GH reserve and insulin resistance indices in all the subjects and in the two groups divided by their GH status
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BMI, body mass index; GHAUC, area under the curve of growth hormone; GHD, growth hormone deficiency; HDL-C, high density lipoprotein cholesterol; IGF-1, insulin-like growth factor-1; LDL-C, low density lipoprotein cholesterol; Peak GH, peak value of growth hormone; WC, waist circumference; WHR, waist-hip ratio.

Analyses were done with Spearman's correlation and bivariate correlation analyses.

The ghrelin and leptin values here in the correlation analysis are log-transformed.

*P < 0.05.

P < 0.01.

References

1. Kojima M, Hosoda H, Date Y. Ghrelin is a growth hormone releasing acylated peptide from stomach. Nature. 1999. 402:656–660.
2. Korbonits M, Goldstone AP, Gueorguiev M, Grossman AB. Ghrelin-a hormone with multiple functions. Front Neuroendocrinol. 2004. 25:27–68.
3. Takaya K, Ariyasu H, Kanamoto N, Iwakura H, Yoshimoto A, Harada M, Mori K, Komatsu Y, Usui T, Shimatsu A, Ogawa Y, Hosoda K, Akamizu T, Kojima M, Kangawa K, Nakao K. Ghrelin strongly stimulates growth hormone release in humans. J Clin Endocrinol Metab. 2000. 85:4908–4911.
4. Ghigo E, Broglio F, Arvat E, Maccario M. Ghrelin: more than a natural GH secretagogue and/or an orexigenic factor. Clin Endocrinol. 2005. 62:1–17.
5. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR. Ghrelin enhances appetitie and increases food intake in humans. J Clin Endocrinol Metab. 2001. 86:5992–5995.
6. Tschop M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes. 2001. 50:707–709.
7. Shintani M, Ogawa Y, Ebihara K, Aizawa-Abe M, Miyanaga F, Takaya K, Hayashi T, Inoue G, Hosoda K, Kojima M, Kangawa K, Nakao K. Ghrelin, an endogenous growth hormone secretagogue ,is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway. Diabetes. 2001. 50:227–232.
8. Ariyase H, Takaya K, Tagami T, Ogawa Y, Hosoda K, Akamizu T, Suda M, Koh T, Natsui K, Toyooka S, Shirakami G, Usui T, Shimatsu A, Doi K, Hosoda H, Kojima M, Kangawa K, Nakao K. Stomach is a major source of circulating ghrelin,and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab. 2001. 86:4753–4758.
9. Choi K, Roh SG, Hong YH, Shrestha YB, Hishikawa D, Chen C, Kojima M, Kangawa K, Sasaki S. The role of ghrelin and growth hormone secretagogues receptor on rat adipogenesis. Endocrinology. 2003. 144:754–759.
10. Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma mk, Dellinger EP, Purnell JQ. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Eng J Med. 2002. 346:1623–1630.
11. Hansen T, Dall R, Hosoda H, Kojima M, Kangawa K, Christiansen JS, Jorgensen JO. Weight loss increases circulating levels of ghrelin in human obesity. Clin Endocrinol. 2002. 56:203–206.
12. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994. 372:425–432.
13. Ursula Meier, Axel M. Endocrine regulation of energy metabolism: Review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin and resistin. Clin Chemistry. 2004. 50:1511–1525.
14. Traebert M, Riediger T, Whitebread S, Scharrer E, Schmid HA. Ghrelin acts on leptin-responsive neurons in the rat arcuate nucleus. J Neuroendocrinol. 2002. 14:580–586.
15. Carroll PV, Christ ER, Bengtsson BA, Carlsson L, Christiansen JS, Clemmons D, Hintz R, Ho K, Laron Z, Sizonenko P, Sonksen PH, Tanaka T, Thorner M. Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. Growth Hormone Research Society Scientific Committee. J Clin Endocrinol Metab. 1998. 83:382–395.
16. De Boer H, Blok GJ, Van der Veen EA. Clinical aspects of growth hormone deficiency in adults. Endocr Rev. 1995. 16:63–86.
17. Dall R, Kanaley J, Hansen TK, Moller N, Christiansen JS, Hosoda H, Kangawa K, Jorgensen JO. Plasma ghrelin levels during exercise in healthy subjects and in growth hormone deficient patients. Eur J Endocrinol. 2002. 147:65–70.
18. Engstrom BE, Burman P, Holdstock C, Karlsson FA. Effects of growth hormone (GH) on ghrelin, leptin and adiponectin in GH-deficient patients. J Clin Endocrinol Metab. 2003. 88:5193–5198.
19. Malik IA, English PJ, Ghatei MA, Bloom SR, MacFarlane IA, Wilding JP. The relationship of ghrelin to biochemical and anthropometric markers of adult growth hormone deficiency. Clin Endocrinol. 2004. 60:137–141.
20. Janssen JA, van der Toorn FM, Hofland LJ, van Koetsveld P, Broglio F, Ghigo E, Lamberts SW, Jan VDL. Systemic ghrelin levels in subjects with growth hormone deficiency are not modified by one year of growth hormone replacement therapy. Eur J Endocrinol. 2001. 145:711–716.
21. Muller AF, Lamberts SW, Janssen JA, Hofland LJ, Koetsveld PV, Bidlngmaier M, Strasburger CJ, Ghigo E, van der Lely AJ. Ghrelin drives GH secretion during fasting in man. Eur J Endocrinol. 2002. 146:203–207.
22. Corbetta S, Peracchi M, Cappiello V. Circulating ghrelin levels in patients with pancreatic and gastrointestinal neuroendocrine tumors: identification of one pancreatic ghrelinoma. J Clin Endocrinol Metab. 2003. 88:3117–3120.
23. Giavoli C, Cappiello V, Corbett S, Ronchi CL, Morpurgo PS, Ferrante E, Beck-Peccoz P, Spada A. Different effects of short-and long-term recombinant hGH administration on ghrelin and adiponectin levels in GH-deficient adults. Clin Endocrinol (Oxf). 2004. 61:81–87.
24. Casaneuva FF, Dieguez C. Neuroendocrine regulation and actions of leptin. Front Neuroendocrinol. 1999. 20:317–363.
25. Al-Shoumet KA, Anyaoku V, Richmond W, Johnston DG. Elevated leptin concentrations growth hormone-deficient hypopituitary adults. Clin Endocrinol (Oxf). 1997. 47:169–171.
26. Fisker S, Vahl N, Hansen T, Jorgensen JO, Hagen C, Orskov H, Christiansen JS. Serum leptin is increased in growth hormone-deficient adults: relationship to body composition and effects of placebo-controlled growth hormone therapy for 1 year. Metabolism. 1997. 46:812–817.
27. Kristensen K, Pedersen SB, Fisker S, Norrelund H, Rosenfalck AM, Jorgensen JOL, Richelsen B. Serum leptin levels and leptin expression in growth hormone(GH)-deficient and healthy adults; influence of GH treatment,gender, and fasting. Metabolism. 1998. 47:1514–1519.
28. Svensson J, Herlitz H, Lundberg B, Johannsson G. Adiponectin, leptin, and erythrocyte sodium/lithium countertransport activity, but not resistin, are related to glucose metabolism in growth hormone deficient adults. J Clin Endocrinol Metab. 2005. 90:2290–2296.
29. Lissett CA, Clayton PE, Shalet SM. The acute leptin response to GH. J Clin Endocrinol Metab. 2001. 86:4412–4415.
30. Kolaczynski JW, Nyce MR, Considine RV, Boden G, Nolan JJ, Henry R, Mudaliar SR, Olefsky J, Caro JF. Acute and chronic effects of insulin on leptin production in humans; Studies in vivo and in vitro. Diabetes. 1996. 45:699–701.
31. Hartman ML, Crowe BJ, Biller BMK, Ho KKY, Clemmons DR, Chipman JJ. on behalf of the HypoCSS Advisory Board and The U.S. HypoCSS Study Group. Which patients do not require a GH stimulation test for the diagnosis of adult GH deficiency? J Clin Endocrinol Metab. 2002. 87:477–485.
32. Lin T, Tucci J. Provocative tests of growth hormone release. Ann Intern Med. 1974. 80:464–469.
33. Eddy RL, Gilliland PF, Ibarra JD Jr, Thompson JQ, MacMurry JF Jr. Human growth hormone release: comparison of provocative test procedures. Am J Med. 1974. 56:179–185.
34. Lissett CA, Thompson EGE, Rahim A, Brennan BMD, Shalet SM. How many tests are required to diagnose growth hormone (GH) deficiency in adults? Clin Endocrinol. 1999. 51:551–557.
35. Toogood AA, O Neill PA, Shalet SM. Beyond the somatopause: growth hormone deficiency in adults over the age of 60 years. J Clin Endocrinol Metab. 1996. 81:460–465.
36. Ghigo E, Aimaretti G, Gianotti L, Bellone J, Arvat E, Camanni F. New approach to the diagnosis of growth hormone deficiency in adults. Eur J Endocrinol. 1996. 134:352–356.
37. Svensson J, Johannsson G, Bengtsson BA. Insulin-like growth factor-I in growth hormone-deficient adults: relationship to population-based normal values, body composition and insulin tolerance test. Clin Endocrinol (Oxf). 1997. 46:579–586.
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Chan-Hee Jung
https://orcid.org/http://orcid.org/0000-0001-8988-0187

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