Journal of Clinical Endocrinology & Metabolism, Vol 75, 762-767, Copyright © 1992 by Endocrine Society

ARTICLES

The effect of anorexia nervosa and refeeding on growth hormone-binding protein, the insulin-like growth factors (IGFs), and the IGF-binding proteins

DR Counts, H Gwirtsman, LM Carlsson, M Lesem and GB Cutler Jr
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.

We studied the relationship of serum insulin-like growth factor-I (IGF- I), IGF-II, the IGF-binding proteins IGFBP-1, IGFBP-2, and IGFBP-3, and GH-binding protein (GHBP; which is postulated to be derived from the extracellular portion of the GH receptor) in normal volunteers and patients with anorexia nervosa before and after a refeeding program. Serum GHBP, IGF-I, and IGFBP-3 were all significantly decreased in low weight patients with anorexia nervosa and returned to nearly normal levels with refeeding. Fasting serum GH and serum IGFBP-1 and IGFBP-2 were significantly increased in low weight patients with anorexia nervosa and also returned to nearly normal levels with refeeding. Serum IGF-II was 27% lower in the low weight group than in normal subjects, but this difference was not statistically significant. Both serum IGF-I and IGF-II were positively correlated with serum IGFBP-3 and negatively correlated with serum IGFBP-1 and IGFBP-2. These data are consistent with the hypothesis that nutritional deprivation alters the GH-IGF axis by down-regulation of the GH receptor or its postreceptor mechanisms, and that this effect is reversible with refeeding.

This article has been cited by other articles:

				E. A. Lawson, K. K. Miller, V. A. Mathur, M. Misra, E. Meenaghan, D. B. Herzog, and A. Klibanski Hormonal and Nutritional Effects on Cardiovascular Risk Markers in Young Women J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3089 - 3094. [Abstract] [Full Text] [PDF]

				M. Misra, K. K. Miller, C. Almazan, M. Worley, D. B. Herzog, and A. Klibanski Hormonal Determinants of Regional Body Composition in Adolescent Girls with Anorexia Nervosa and Controls J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2580 - 2587. [Abstract] [Full Text] [PDF]

				H. K. Gleeson, C. A. Lissett, and S. M. Shalet Insulin-Like Growth Factor-I Response to a Single Bolus of Growth Hormone Is Increased in Obesity J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1061 - 1067. [Abstract] [Full Text] [PDF]

				S. Grinspoon, K. K. Miller, D. B. Herzog, K. A. Grieco, and A. Klibanski Effects of Estrogen and Recombinant Human Insulin-Like Growth Factor-I on Ghrelin Secretion in Severe Undernutrition J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3988 - 3993. [Abstract] [Full Text] [PDF]

				T. Tagami, N. Satoh, T. Usui, K. Yamada, A. Shimatsu, and H. Kuzuya Adiponectin in Anorexia Nervosa and Bulimia Nervosa J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1833 - 1837. [Abstract] [Full Text] [PDF]

				M. Misra, K. K. Miller, J. Bjornson, A. Hackman, A. Aggarwal, J. Chung, M. Ott, D. B. Herzog, M. L. Johnson, and A. Klibanski Alterations in Growth Hormone Secretory Dynamics in Adolescent Girls with Anorexia Nervosa and Effects on Bone Metabolism J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5615 - 5623. [Abstract] [Full Text] [PDF]

				M. Misra, L. A Soyka, K. K Miller, S. Grinspoon, L. L Levitsky, and A. Klibanski Regional body composition in adolescents with anorexia nervosa and changes with weight recovery Am. J. Clinical Nutrition, June 1, 2003; 77(6): 1361 - 1367. [Abstract] [Full Text] [PDF]

				S. Grinspoon, K. Miller, D. Herzog, D. Clemmons, and A. Klibanski Effects of Recombinant Human Insulin-Like Growth Factor (IGF)-I and Estrogen Administration on IGF-I, IGF Binding Protein (IGFBP)-2, and IGFBP-3 in Anorexia Nervosa: A Randomized-Controlled Study J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1142 - 1149. [Abstract] [Full Text] [PDF]

				V. Tolle, M. Kadem, M.-T. Bluet-Pajot, D. Frere, C. Foulon, C. Bossu, R. Dardennes, C. Mounier, P. Zizzari, F. Lang, et al. Balance in Ghrelin and Leptin Plasma Levels in Anorexia Nervosa Patients and Constitutionally Thin Women J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 109 - 116. [Abstract] [Full Text] [PDF]

				D. Mesotten, P. J. D. Delhanty, F. Vanderhoydonc, K. V. Hardman, F. Weekers, R. C. Baxter, and G. van den Berghe Regulation of Insulin-Like Growth Factor Binding Protein-1 during Protracted Critical Illness J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5516 - 5523. [Abstract] [Full Text] [PDF]

				C. M. Gordon, E. Grace, S. J. Emans, H. A. Feldman, E. Goodman, K. A. Becker, C. J. Rosen, C. M. Gundberg, and M. S. LeBoff Effects of Oral Dehydroepiandrosterone on Bone Density in Young Women with Anorexia Nervosa: A Randomized Trial J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 4935 - 4941. [Abstract] [Full Text] [PDF]

				M. S. Sandhu, D. B. Dunger, and E. L. Giovannucci Insulin, Insulin-Like Growth Factor-I (IGF-I), IGF Binding Proteins, Their Biologic Interactions, and Colorectal Cancer J Natl Cancer Inst, July 3, 2002; 94(13): 972 - 980. [Abstract] [Full Text] [PDF]

				S. Grinspoon, L. Thomas, K. Miller, D. Herzog, and A. Klibanski Effects of Recombinant Human IGF-I and Oral Contraceptive Administration on Bone Density in Anorexia Nervosa J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2883 - 2891. [Abstract] [Full Text] [PDF]

				L. E. L. Katz, D. D. DeLeon, H. Zhao, and A. F. Jawad Free and Total Insulin-Like Growth Factor (IGF)-I Levels Decline during Fasting: Relationships with Insulin and IGF-Binding Protein-1 J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2978 - 2983. [Abstract] [Full Text] [PDF]

				E. Giovannucci Insulin, Insulin-Like Growth Factors and Colon Cancer: A Review of the Evidence J. Nutr., November 1, 2001; 131(11): 3109S - 3120. [Abstract] [Full Text] [PDF]

				R. Kaaks, S. Soderberg, T. Olsson, G. Hallmans, and P. Stattin RESPONSE: Re: Plasma Insulin-Like Growth Factor-I, Insulin-Like Growth Factor-Binding Proteins, and Prostate Cancer Risk: a Prospective Study J Natl Cancer Inst, April 18, 2001; 93(8): 650 - 651. [Full Text] [PDF]

				G. A. Kaysen Malnutrition and the acute-phase reaction in dialysis patients--how to measure and how to distinguish Nephrol. Dial. Transplant., October 1, 2000; 15(10): 1521 - 1524. [Full Text] [PDF]

				L. Gianotti, A. I. Pincelli, M. Scacchi, M. Rolla, D. Bellitti, E. Arvat, F. Lanfranco, A. Torsello, E. Ghigo, F. Cavagnini, et al. Effects of Recombinant Human Insulin-Like Growth Factor I Administration on Spontaneous and Growth Hormone (GH)-Releasing Hormone-Stimulated GH Secretion in Anorexia Nervosa J. Clin. Endocrinol. Metab., August 1, 2000; 85(8): 2805 - 2809. [Abstract] [Full Text]

				V. BRUNI, M. DEI, I. VICINI, L. BENINATO, and L. MAGNANI Estrogen Replacement Therapy in the Management of Osteopenia Related to Eating Disorders Ann. N.Y. Acad. Sci., April 1, 2000; 900(1): 416 - 421. [Abstract] [Full Text] [PDF]

				T. Amit, M. B. H. Youdim, and Z.'e. Hochberg Does Serum Growth Hormone (GH) Binding Protein Reflect Human GH Receptor Function? J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 927 - 932. [Abstract] [Full Text]

				M. Hotta, I. Fukuda, K. Sato, N. Hizuka, T. Shibasaki, and K. Takano The Relationship between Bone Turnover and Body Weight, Serum Insulin-Like Growth Factor (IGF) I, and Serum IGF-Binding Protein Levels in Patients with Anorexia Nervosa J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 200 - 206. [Abstract] [Full Text]

				A. Maxwell, R. Butterwick, R. M. Batt, and C. Camacho-Hübner Serum Insulin-Like Growth Factor (IGF)-I Concentrations Are Reduced by Short-Term Dietary Restriction and Restored by Refeeding in Domestic Cats (Felis catus) J. Nutr., October 1, 1999; 129(10): 1879 - 1884. [Abstract] [Full Text]

				I. Fukuda, M. Hotta, N. Hizuka, K. Takano, Y. Ishikawa, K. Asakawa-Yasumoto, E. Tagami, and H. Demura Decreased Serum Levels of Acid-Labile Subunit in Patients with Anorexia Nervosa J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2034 - 2036. [Abstract] [Full Text]

				S. Grinspoon, K. Miller, C. Coyle, J. Krempin, C. Armstrong, S. Pitts, D. Herzog, and A. Klibanski Severity of Osteopenia in Estrogen-Deficient Women with Anorexia Nervosa and Hypothalamic Amenorrhea J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2049 - 2055. [Abstract] [Full Text]

				R. K. Støving, J. D. Veldhuis, A. Flyvbjerg, J. Vinten, J. Hangaard, O. G. Koldkjær, J. Kristiansen, and C. Hagen Jointly Amplified Basal and Pulsatile Growth Hormone (GH) Secretion and Increased Process Irregularity in Women with Anorexia Nervosa: Indirect Evidence for Disruption of Feedback Regulation within the GH-Insulin-Like Growth Factor I Axis J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2056 - 2063. [Abstract] [Full Text]

				R. K. Støving, A. Flyvbjerg, J. Frystyk, S. Fisker, J. Hangaard, M. Hansen-Nord, and C. Hagen Low Serum Levels of Free and Total Insulin-Like Growth Factor I (IGF-I) in Patients with Anorexia Nervosa Are Not Associated with Increased IGF-Binding Protein-3 Proteolysis J. Clin. Endocrinol. Metab., April 1, 1999; 84(4): 1346 - 1350. [Abstract] [Full Text]

				B M D Brennan, M Gill, L Pennells, O B Eden, A G Thomas, and P E Clayton Insulin-like growth factor I, IGF binding protein 3, and IGFBP protease activity: relation to anthropometric indices in solid tumours or leukaemia Arch. Dis. Child., March 1, 1999; 80(3): 226 - 230. [Abstract] [Full Text]

				L. E. Underwood Special Considerations in the Design of Trials Involving Children J. Nutr., January 1, 1999; 129(1): 264S - 264S. [Full Text] [PDF]

				M. A. Llopis, M. L. Granada, G. Cuatrecasas, X. Formiguera, L. Sánchez-Planell, A. SanmartÍ, A. Alastrué, M. Rull, A. Corominas, and M. Foz Growth Hormone-Binding Protein Directly Depends on Serum Leptin Levels in Adults with Different Nutritional Status J. Clin. Endocrinol. Metab., June 1, 1998; 83(6): 2006 - 2011. [Abstract] [Full Text]

				E. D. Eckert, C. Pomeroy, N. Raymond, P. F. Kohler, P. Thuras, and C. Y. Bowers Leptin in Anorexia Nervosa J. Clin. Endocrinol. Metab., March 1, 1998; 83(3): 791 - 795. [Abstract] [Full Text]

				A. B. Loucks, M. Verdun, and E. M. Heath Low energy availability, not stress of exercise, alters LH pulsatility in exercising women J Appl Physiol, January 1, 1998; 84(1): 37 - 46. [Abstract] [Full Text] [PDF]

				G. A. Laughlin, C. E. Dominguez, and S. S. C. Yen Nutritional and Endocrine-Metabolic Aberrations in Women with Functional Hypothalamic Amenorrhea J. Clin. Endocrinol. Metab., January 1, 1998; 83(1): 25 - 32. [Abstract] [Full Text]

				S. Rajaram, D. J. Baylink, and S. Mohan Insulin-Like Growth Factor-Binding Proteins in Serum and Other Biological Fluids: Regulation and Functions Endocr. Rev., December 1, 1997; 18(6): 801 - 831. [Abstract] [Full Text]

				W. J. Smith, L. E. Underwood, L. Keyes, and D. R. Clemmons Use of Insulin-Like Growth Factor I (IGF-I) and IGF-Binding Protein Measurements to Monitor Feeding of Premature Infants J. Clin. Endocrinol. Metab., December 1, 1997; 82(12): 3982 - 3988. [Abstract] [Full Text] [PDF]

				C. Heinrichs, M. Colli, J. A. Yanovski, L. Laue, N. A. Gerstl, A. D. Kramer, J. A. Uyeda, and J. Baron Effects of Fasting on the Growth Plate: Systemic and Local Mechanisms Endocrinology, December 1, 1997; 138(12): 5359 - 5365. [Abstract] [Full Text] [PDF]

				B. Boersma and J. M. Wit Catch-up Growth Endocr. Rev., October 1, 1997; 18(5): 646 - 661. [Abstract] [Full Text]

				M. Scacchi, A. I. Pincelli, A. Caumo, P. Tomasi, G. Delitala, G. Baldi, and F. Cavagnini Spontaneous Nocturnal Growth Hormone Secretion in Anorexia Nervosa J. Clin. Endocrinol. Metab., October 1, 1997; 82(10): 3225 - 3229. [Abstract] [Full Text] [PDF]

				J. Argente, N. Caballo, V. Barrios, M. T. Munoz, J. Pozo, J. A. Chowen, G. Morande, and M. Hernandez Multiple Endocrine Abnormalities of the Growth Hormone and Insulin-Like Growth Factor Axis in Patients with Anorexia Nervosa: Effect of Short- and Long-Term Weight Recuperation J. Clin. Endocrinol. Metab., July 1, 1997; 82(7): 2084 - 2092. [Abstract] [Full Text] [PDF]

				J. N. Roemmich and W. E. Sinning Weight loss and wrestling training: effects on growth-related hormones J Appl Physiol, June 1, 1997; 82(6): 1760 - 1764. [Abstract] [Full Text] [PDF]

				B. Tonshoff, M. J. Cronin, M. Reichert, D. Haffner, A.-M. Wingen, W. F. Blum, and O. Mehls Reduced Concentration of Serum Growth Hormone (GH)-Binding Protein in Children with Chronic Renal Failure: Correlation with GH Insensitivity J. Clin. Endocrinol. Metab., April 1, 1997; 82(4): 1007 - 1013. [Abstract] [Full Text] [PDF]

				M. Boguszewski, R. Bjarnason, S. Rosberg, L. M. S. Carlsson, and K. Albertsson-Wikland Growth Hormone (GH)-Binding Protein in Prepubertal Short Children Born Small for Gestational Age: Effects of Growth Hormone Treatment J. Clin. Endocrinol. Metab., April 1, 1997; 82(4): 1014 - 1019. [Abstract] [Full Text] [PDF]

				C. A. M. Roelen, H. P. F. Koppeschaar, W. R. de Vries, Y. E. M. Snel, M. E. Doerga, P. M. J. Zelissen, J. H. H. Thijssen, and M. A. Blankenstein Visceral Adipose Tissue Is Associated with Circulating High Affinity Growth Hormone-Binding Protein J. Clin. Endocrinol. Metab., March 1, 1997; 82(3): 760 - 764. [Abstract] [Full Text] [PDF]

				S. Fisker, N. Vahl, J. O. L. Jorgensen, J. S. Christiansen, and H. Orskov Abdominal Fat Determines Growth Hormone-Binding Protein Levels in Healthy Nonobese Adults J. Clin. Endocrinol. Metab., January 1, 1997; 82(1): 123 - 128. [Abstract] [Full Text] [PDF]