The changes in serum leptin levels during growth hormone (GH) treatment were studied in 27 children, 17 with GH deficiency (GHD), 10 with idiopathic short stature (ISS), and 9 with Prader-Willi syndrome (PWS). Within 1 month of GH treatment, serum leptin levels decreased by 40% in the GHD children (p < 0.01). There was no significant change in serum leptin level in the children with ISS. In children with PWS, the mean serum leptin level decreased by almost 60% after 3 months of treatment (p < 0.001). Thereafter, no further decline was observed in any of the 3 groups. Changes in body composition became evident first after the 3 months of treatment. In the GHD children, the BMI was unchanged while the mean body fat percentage was 2.7% lower after 1 year of GH treatment (p < 0.05). In the ISS children, neither BMI nor body fat percentage were significantly changed during treatment. The PWS children exhibited a significant decrease in BMI after 6 months of GH treatment without any further change during the remaining period of treatment. In this group, the mean body fat percentage decreased from 42 ± 2.4 to 28 ± 2.2% after treatment (p < 0.001). The finding that the fall in leptin occurs before changes in body composition become detectable suggests a direct effect of GH on leptin production, metabolism, or clearance.

Keywords:
Prader-Willi syndrome, Short stature, Idiopathic, Growth hormone deficiency, Children, Leptin, Growth hormone, Body fat percentage, Body mass index
1.
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.
2.
Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, Richards GJ, Campfield LA, Clark FT, Deeds J, et al: Identification and expression cloning of a leptin receptor, OB-R. Cell 1995;83:1263–1271.
3.
Rohner-Jeanrenaud F, Jeanrenaud B: Obesity, leptin, and the brain. N Engl J Med 1996;334:324–325.
4.
Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, Sewter CP, Digby JE, Mohammed SN, Hurst JA, Cheetham CH, Earley AR, Barnett AH, Prins JB, O’Rahilly S: Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997;387:903–908.
5.
Clement K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, Gourmelen M, Dina C, Chambaz J, Lacorte JM, Basdevant A, Bougneres P, Lebouc Y, Froguel P, Guy-Grand B: A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 1998;392:398–401.
6.
Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S, et al: Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1995;1:1155–1161.
7.
Friedman JM, Halaas JL: Leptin and the regulation of body weight in mammals. Nature 1998;395:763–770.
8.
Kolaczynski JW, Considine RV, Ohannesian J, Marco C, Opentanova I, Nyce MR, Myint M, Caro JF: Responses of leptin to short-term fasting and refeeding in humans: A link with ketogenesis but not ketones themselves. Diabetes 1996;45:1511–1515.
9.
Elimam A, Knutsson U, Brönnegård M, Stierna P, Albertsson-Wikland K, Marcus C: Variation in glucocorticoids within the physiological range affect plasma leptin levels. Eur J Endocrinol 1998;139:615–620.
10.
Miell JP, Englaro P, Blum WF: Dexamethasone induces an acute and sustained rise in circulating leptin levels in normal human subjects. Horm Metab Res 1996;28:704–707.
11.
Larsson H, Ahren B: Short-term dexamethasone treatment increases plasma leptin independently of changes in insulin sensitivity in healthy women. J Clin Endocrinol Metab 1996;81:4428–4432.
12.
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.
13.
Saad MF, Khan A, Sharma A, Michael R, Riad-Gabriel MG, Boyadjian R, Jinagouda SD, Steil GM, Kamdar V: Physiological insulinemia acutely modulates plasma leptin. Diabetes 1998;47:544–549.
14.
Utriainen T, Malmstrom R, Makimattila S, Yki-Jarvinen H: Supraphysiological hyperinsulinemia increases plasma leptin concentrations after 4 h in normal subjects. Diabetes 1996;45:1364–1366.
15.
Valcavi R, Zini M, Peino R, Casanueva FF, Dieguez C: Influence of thyroid status on serum immunoreactive leptin levels. J Clin Endocrinol Metab 1997;82:1632–1634.
16.
Yoshida T, Momotani N, Hayashi M, Monkawa T, Ito K, Saruta T: Serum leptin concentrations in patients with thyroid disorders. Clin Endocrinol 1998;48:299–302.
17.
Mantzoros CS, Rosen HN, Greenspan SL, Flier JS, Moses AC: Short-term hyperthyroidism has no effect on leptin levels in man. J Clin Endocrinol Metab 1997;82:497–499.
18.
Chen XL, Hausman DB, Dean RG, Hausman GJ: Hormonal regulation of leptin mRNA expression and preadipocyte recruitment and differentiation in porcine primary cultures of S-V cells. Obes Res 1998;6:164–172.
19.
Hardie LJ, Guilhot N, Trayhurn P: Regulation of leptin production in cultured mature white adipocytes. Horm Metab Res 1996;28:685–689.
20.
Böni-Schnetzler M, Gosteli-Peter MA, Moritz W, Froesch ER, Zapf J: Reduced ob mRNA in hypophysectomised rats is not restored by growth hormone (GH), but further suppressed by exogenously administered insulin-like growth factor (IGF) 1. Biochem Biophys Res Commun 1996;225:296–301.
21.
al-Shoumer KA, Anyaoku V, Richmond W, Johnston DG: Elevated leptin concentrations in growth hormone-deficient hypopituitary adults. Clin Endocrinol 1997;47:153–159.
22.
Janssen YJ, Frolich M, Deurenberg P, Roelfsema F: Serum leptin levels during recombinant human GH therapy in adults with GH deficiency. Eur J Endocrinol 1997;137:650–654.
23.
Fisker S, Vahl N, Hansen TB, 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.
24.
Florkowski CM, Collier GR, Zimmet PZ, Livesey JH, Espiner EA, Donald RA: Low-dose growth hormone replacement lowers plasma leptin and fat stores without affecting body mass index in adults with growth hormone deficiency. Clin Endocrinol 1996;45:769–773.
25.
Nystrom F, Ekman B, Osterlund M, Lindstrom T, Ohman KP, Arnqvist HJ: Serum leptin concentrations in a normal population and in GH deficiency: Negative correlation with testosterone in men and effects of GH treatment. Clin Endocrinol 1997;47:191–198.
26.
Rauch F, Westermann F, Englaro P, Blum WF, Schonau E: Serum leptin is suppressed by growth hormone therapy in growth hormone-deficient children. Horm Res 1998;50:18–21.
27.
Bianda TL, Glatz Y, Boeni-Schnetzler M, Froesch ER, Schmid C: Effects of growth hormone (GH) and insulin-like growth factor-I on serum leptin in GH-deficient adults (letter). Diabetologia 1997;40:363–364.
28.
Holm VA, Cassidy SB, Butler MG, Hanchett JM, Greenswag LR, Whitman BY, Greenberg F: Prader-Willi syndrome: Consensus diagnostic criteria. Pediatrics 1993;91:398–340.
29.
Juul A, Bang P, Hertel NT, Main K, Dalgaard P, Jorgensen K, Muller J, Hall K, Skakkebaek NE: Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults: Relation to age, sex, stage of puberty, testicular size, and body mass index. J Clin Endocrinol Metab 1994;78:744–752.
30.
Rolland-Cachera M, Sempe M, Guilloud-Bataille M, Patois E, Pequignot-Guggenbühl F, Fautrad V: Adiposity indices in children. Am J Clin Nutr 1982;36:178–184.
31.
Gill MS, Toogood AA, Jones J, Clayton PE, Shalet SM: Serum leptin response to the acute and chronic administration of growth hormone (GH) to elderly subjects with GH deficiency. J Clin Endocrinol Metab 1999;84:1288–1295.
32.
Karlsson C, Stenlof K, Johannsson G, Marin P, Bjorntorp P, Bengtsson BA, Carlsson B, Carlsson LM, Sjostrom L: Effects of growth hormone treatment on the leptin system and on energy expenditure in abdominally obese men. Eur J Endocrinol 1998;138:408–414.
33.
Tanner JM, Hughes PC, Whitehouse RH: Comparative rapidity of response of height, limb muscle and limb fat to treatment with human growth hormone in patients with and without growth hormone deficiency. Acta Endocrinol 1977;84:681–696.
34.
Kristrom B, Carlsson B, Rosberg S, Carlsson LM, Albertsson-Wikland K: Short-term changes in serum leptin levels provide a strong metabolic marker for the growth response to growth hormone treatment in children. Swedish Study Group for Growth Hormone Treatment. J Clin Endocrinol Metab 1998;83:2735–2741.
35.
Boguszewski M, Dahlgren J, Bjarnason R, Rosberg S, Carlsson LM, Carlsson B, Albertsson-Wikland K: Serum leptin in short children born small for gestational age: Relationship with the growth response to growth hormone treatment. The Swedish Study Group for Growth Hormone Treatment. Eur J Endocrinol 1997;137:387–395.
36.
Martha PM Jr, Reiter EO, Davila N, Shaw MA, Holcombe JH, Baumann G: The role of body mass in the response to growth hormone therapy. J Clin Endocrinol Metab 1992;75:1470–1473.
37.
Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, et al: Serum immunoreactive leptin concentrations in normal-weight and obese humans. N Engl J Med 1996;334:292–295.
38.
Lonnqvist F, Arner P, Nordfors L, Schalling M: Overexpression of the obese (ob) gene in adipose tissue of human obese subjects. Nat Med 1995;1:950–953.
39.
Vanderschueren-Lodeweyckx M: The effect of simple obesity on growth and growth hormone. Horm Res 1993;40:23–30.
40.
Martha PM Jr, Gorman KM, Blizzard RM, Rogol AD, Veldhuis JD: Endogenous growth hormone secretion and clearance rates in normal boys, as determined by deconvolution analysis: Relationship to age, pubertal status, and body mass. J Clin Endocrinol Metab 1992;74:336–344.
41.
Wadden TA, Considine RV, Foster GD, Anderson DA, Sarwer DB, Caro JS: Short- and long-term changes in serum leptin dieting obese women: Effects of caloric restriction and weight loss. J Clin Endocrinol Metab 1998;83:214–218.
42.
Weigle DS, Duell PB, Connor WE, Steiner RA, Soules MR, Kuijper JL: Effect of fasting, refeeding, and dietary fat restriction on plasma leptin levels. J Clin Endocrinol Metab 1997;82:561–565.
43.
Hartman ML, Veldhuis JD, Johnson ML, Lee MM, Alberti KG, Samojlik E, Thorner MO: Augmented growth hormone (GH) secretory burst frequency and amplitude mediate enhanced GH secretion during a two-day fast in normal men. J Clin Endocrinol Metab 1992;74:757–765.
44.
Klein S, Coppack SW, Mohamed-Ali V, Landt M: Adipose tissue leptin production and plasma leptin kinetics in humans. Diabetes 1996;45:984–987.
45.
Meyer C, Robson D, Rackovsky N, Nadkarni V, Gerich J: Role of the kidney in human leptin metabolism. Am J Physiol 1997;273:E903–E907.
46.
Garibotto G, Russo R, Franceschini R, Robaudo C, Saffioti S, Sofia A, Rolandi E, Deferrari G, Barreca T: Inter-organ leptin exchange in humans. Biochem Biophys Res Commun 1998;247:504–509.
47.
Cumin F, Baum HP, Levens N: Mechanism of leptin removal from the circulation by the kidney. J Endocrinol 1997;155:577–585.
48.
Hammerman MR: The growth hormone-insulin-like growth factor axis in kidney. Am J Physiol 1989;257:F503–F508.
49.
Kamel A, Margery V, Norstedt G, Thoren M, Lindgren AC, Bronnegard M, Marcus C: 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.
50.
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.
51.
Hirschberg R, Rabb H, Bergamo R, Kopple J: The delayed effect of growth hormone on renal function in humans. Kidney Internatioal 1989;35:865–868.
52.
Holt RI, Crossey PA, Jones JS, Baker AJ, Portmann B, Miell JP: Hepatic growth hormone receptor, insulin-like growth factor I, and insulin-like growth factor-binding protein messenger RNA expression in pediatric liver disease. Hepatology 1997;26:1600–1606.
53.
Hermansson M, Wickelgren RB, Hammarqvist F, Bjarnason R, Wennstrom I, Wernerman J, Carlsson B, Carlsson LM: Measurement of human growth hormone receptor messenger ribonucleic acid by a quantitative polymerase chain reaction-based assay: Demonstration of reduced expression after elective surgery. J Clin Endocrinol Metab 1997;82:421–428.
© 2000 S. Karger AG, Basel
2000
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.