Serum ghrelin and leptin concentrations in children with cancer : comparisons with normal children

소아 종양 환아의 혈중 Ghrelin과 Leptin의 농도: 정상 소아와 비교

  • Park, So Hyun (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Jung, Min Ho (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Chung, Nac Gyun (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Suh, Byung-Kyu (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Lee, Byung Churl (Department of Pediatrics, College of Medicine, The Catholic University of Korea)
  • 박소현 (가톨릭대학교 의과대학 소아과학교실) ;
  • 정민호 (가톨릭대학교 의과대학 소아과학교실) ;
  • 정낙균 (가톨릭대학교 의과대학 소아과학교실) ;
  • 서병규 (가톨릭대학교 의과대학 소아과학교실) ;
  • 이병철 (가톨릭대학교 의과대학 소아과학교실)
  • Received : 2007.06.22
  • Accepted : 2007.08.03
  • Published : 2007.09.15

Abstract

Purpose : Ghrelin, being secreted from the stomach, stimulates growth hormone secretion and controls energy homeostasis by increasing appetite. Leptin, being secreted from the adipocytes, controls weight and energy homeostasis by decreasing appetite. Leptin concentration is reported to increase after childhood cancer therapy. This study was aimed to compare ghrelin and leptin concentrations in normal children and children who received cancer therapy. Methods : We enrolled forty-three patients who were diagnosed with cancer and received radiotherapy or chemotherapy during Dec. 2004 through Dec. 2005 in St. Marys hospital and Kangnam St. Marys hospital. Forty-five healthy children were selected as a control group whose age, gender, weight and height were similar to those of cancer group. The serum leptin and ghrelin concentrations were also measured by radioimmunoassay. Results : The cancer group showed higher BMI and leptin concentrations. The control group showed higher concentrations of ghrelin. Both control and cancer groups revealed positive correlations between leptin concentrations and BMI. Ghrelin concentrations in the control group showed negative correlations with age, height, weight and BMI but no significant correlation was found in the cancer group. All the parameters in the group treated with chemotherapy only were not different from those in the group treated with chemotherapy and irradiation. But the level of ghrelin in the acute myeloid leukemia group was much higher than those in the acute lymphoblastic leukemia group. Conclusion : Patients with pediatric cancer treatment have presented higher BMI and leptin concentrations but lower ghrelin concentrations than those in healthy children. Because of the relatively short duration and cross sectional method of the study, however, further long term and prospective study will be required in the future.

목 적 : Ghrelin은 위에서 주로 분비되는 펩타이드로, 성장호르몬의 분비를 촉진시키고, 식욕을 증가시켜 에너지 균형을 조절한다고 알려져 있으며, leptin은 지방세포에서 분비되어 식욕을 억제시키는 작용을 통해 체중 및 에너지 대사에 관여한다. 저자들은 소아 종양으로 진단받고 항암 요법중인 환아의 ghrelin과 leptin 농도를 정상아와 비교해 보았다. 방 법 : 2003년 12월부터 2004년 12월까지 강남 성모병원과 성모병원에서 소아 종양을 진단 받고 방사선 조사나 항암 화학요법을 받은 환아들 중 43명(남아 31명, 여아 12명)을 대상으로 하였으며, 환아군과 성별, 나이, 체중 및 신장이 비슷한 건강한 소아 45명(남아 26명, 여아 19명)을 대조군으로 하였다. 대상아들의 혈중 leptin과 ghrelin 농도를 방사면역측정법으로 측정하였다. 결 과 : 환아군과 대조군에서 BMI와 leptin 농도는 환아군에서 더 높았으며, ghrelin은 대조군에서 더 높았다. 또한 leptin 농도는 환아군(r=0.61, P<0.05)과 대조군(r=0.40, P<0.05) 모두에서 BMI와 양의 상관관계가 있었다. ghrelin 농도는 정상군에서는 연령, 신장, 체중 및 BMI와 음의 상관관계를 보였으나 환아군에서는 의미있는 상관관계는 없었다. 한편, 방사선요법을 받은 군과 화학요법만을 받은 군으로 나누어 비교했을 때에는 두 군간의 의미있는 차이는 없었으며, 급성 골수성 백혈병군과 급성 림프구성 백혈병군으로 나누었을 때 ghrelin의 농도가 골수성 백혈병군에서 훨씬 높았다. 결 론 : 소아 종양으로 항암 요법을 받고 있는 환아는 정상아에 비해 BMI가 더 높고, leptin 농도도 더 높았으나, ghrelin 농도는 더 낮았다. 그러나 본 연구가 한 시점에서의 단기적이고 단편적인 연구이므로 추후 오랜 기간에 걸친 전향적인 연구가 더 필요하다고 생각된다.

Keywords

References

  1. Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ. Cancer statistics. CA Cancer J Clin 2003;53:5-26 https://doi.org/10.3322/canjclin.53.1.5
  2. Bhatia S, Landier W, Robison LL. Late effects of childhood cancer therapy. In DeVita VT, Hellman S, Rosenberg SA, editors. Progress in oncology 2002. Boston: Jones and Bartlett Publishers 2002:171-201
  3. Jarfelt M, Lannering B, Bosaeus I, Johannsson G, Bjarnason R. Body composition in young adult survivors of childhood acute lymphoblastic leukaemia. Eur J Endocrinol 2005;153: 81-9 https://doi.org/10.1530/eje.1.01931
  4. Kourti M, Tragiannidis A, Makedou A, Papageorgiou T, Rousso I, Athanassiadou F. Metabolic syndrome in children and adolescents with acute lymphoblastic leukemia after the completion of chemotherapy. J Pediatr Hematol Oncol 2005; 27:499-501 https://doi.org/10.1097/01.mph.0000181428.63552.e9
  5. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999;402:656-60 https://doi.org/10.1038/45230
  6. Tschop M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes 2001;50:707-9 https://doi.org/10.2337/diabetes.50.4.707
  7. Otto B, Cuntz U, Fruehauf E, Wawarta R, Folwaczny C, Riepl RL, et al. Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa. Eur J Endocrinol 2001;145:669-73 https://doi.org/10.1530/eje.0.1450669
  8. Takaya K, Ariyasu H, Kanamoto N, Iwakura H, Yoshimoto A, Harada M, et al. Ghrelin strongly stimulates growth hormone release in humans. J Clin Endocrinol Metab 2000; 85:4908-11 https://doi.org/10.1210/jc.85.12.4908
  9. Flier JS. Clinical review 94: Whats in a name? In search of leptins physiologic role. J Clin Endocrinol Metab 1998;83: 1407-13 https://doi.org/10.1210/jc.83.5.1407
  10. Tsiotra PC, Pappa V, Koukourava A, Economopoulos T, Tsigos C, Raptis SA. Expression of leptin receptors in mononuclear cells from myelodysplastic syndromes and acute myeloid leukemias. Acta Haematol 2005;114:71-7 https://doi.org/10.1159/000086578
  11. Davies JH, Evans BA, Jones E, Evans WD, Jenney ME, Gregory JW. Osteopenia, excess adiposity and hyperleptinaemia during 2 years of treatment for childhood acute lymphoblastic leukaemia without cranial irradiation. Clin Endocrinol (Oxf) 2004;60:358-65 https://doi.org/10.1111/j.1365-2265.2003.01986.x
  12. Brennan BM, Rahim A, Blum WF, Adams JA, Eden OB, Shalet SM. Hyperleptinaemia in young adults following cranial irradiation in childhood: growth hormone deficiency or leptin insensitivity? Clin Endocrinol (Oxf) 1999;50:163-9 https://doi.org/10.1046/j.1365-2265.1999.00622.x
  13. Corbetta S, Peracchi M, Cappiello V, Lania A, Lauri E, Vago L, et al. Circulating ghrelin levels in patients with pancreatic and gastrointestinal neuroendocrine tumors: identification of one pancreatic ghrelinoma. J Clin Endocrinol Metab 2003;88:3117-20 https://doi.org/10.1210/jc.2002-021842
  14. Martinez-Fuentes AJ, Moreno-Fernandez J, Vazquez-Martinez R, Duran-Prado M, de la Riva A, Tena-Sempere M, et al. Ghrelin is produced by and directly activates corticotrope cells from adrenocorticotropin-secreting adenomas. J Clin Endocrinol Metab 2006;91:2225-31 https://doi.org/10.1210/jc.2006-0235
  15. Camurdan MO, Bideci A. Demirel F, Cinaz P. Serum ghrelin, IGF-1 and IGFBP-3 levels in children with normal variant short stature. Endocr J 2006;53:479-84 https://doi.org/10.1507/endocrj.K05-167
  16. Jo DS, Lee JU, Kim SY, Kim SJ, Kang CW, Hwang PH, et al. J Korean Soc Pediatr Endocrinol 2004;9:179-85
  17. Nishi Y, Isomoto H, Ueno H, Ohnita K, Wen CY, Takeshima F, et al. Plasma leptin and ghrelin concentrations in patients with Crohns disease. World J Gastroenterol 2005;11:7314-7 https://doi.org/10.3748/wjg.v11.i46.7314
  18. Otero M, Nogueiras R, Lago F, Dieguez C, Gomez-Reino JJ, Gualillo O. Chronic inflammation modulates ghrelin levels in humans and rats. Rheumatology (Oxford) 2004;43:306-10 https://doi.org/10.1093/rheumatology/keh055
  19. Volante M, Allia E, Gugliotta P, Funaro A, Broglio F, Deghenghi R, et al. Expression of ghrelin and of the GH secretagogue receptor by pancreatic islet cells and related endocrine tumors. J Clin Endocrinol Metab 2002;87:1300-8 https://doi.org/10.1210/jc.87.3.1300
  20. De Vriese C, Gregoire F, De Neef P, Robberecht P, Delporte C. Ghrelin is produced by the human erythroleukemic HEL cell line and involved in an autocrine pathway leading to cell proliferation. Endocrinology 2005;146:1514-22 https://doi.org/10.1210/en.2004-0964
  21. Hattori N, Saito T, Yagyu T, Jiang BH, Kitagawa K, Inagaki C. GH, GH receptor, GH secretagogue receptor, and ghrelin expression in human T cells, B cells, and neutrophils. J Clin Endocrinol Metab 2001;86:4284-91 https://doi.org/10.1210/jc.86.9.4284
  22. Whatmore AJ, Hall CM, Jones J, Westwood M, Clayton PE. Ghrelin concentrations in healthy children and adolescents. Clin Endocrinol (Oxf) 2003;59:649-54 https://doi.org/10.1046/j.1365-2265.2003.01903.x
  23. Mann DR, Johnson AO, Gimpel T, Castracane VD. Changes in circulating leptin, leptin receptor, and gonadal hormones from infancy until advanced age in humans. J Clin Endocrinol Metab 2003;88:3339-45 https://doi.org/10.1210/jc.2002-022030
  24. Bunt JC, Salbe AD, Tschop MH, DelParigi A, Daychild P, Tataranni PA. Cross-sectional and prospective relationships of fasting plasma ghrelin concentrations with anthropometric measures in Pima Indian children. J Clin Endocrinol Metab 2003;88:3756-61 https://doi.org/10.1210/jc.2003-030227
  25. Konopleva M, Mikhail A, Estrov Z, Zhao S, Harris D, Sanchez- Williams G, et al. Expression and function of leptin receptor isoforms in myeloid leukemia and myelodysplastic syndromes: proliferative and anti-apoptotic activities. Blood 1999;93:1668-76
  26. Muszynska-Roslan K, Krawczuk-Rybak M, Topczewska M, Sawicka-Zukowska M. Relationship between body mass index and leptin levels in children treated for acute lymphoblastic leukemia during and after maintenance therapy. Endokrynol Diabetol Chor Przemiany Materii Wieku Rozw. 2006;12:91-5