Elsevier

Metabolism

Volume 41, Issue 1, January 1992, Pages 106-112
Metabolism

The distal axis of growth hormone (GH) in nutritional disorders: GH-binding protein, insulin-like growth factor-I (IGF-I), and IGF-I receptors in obesity and anorexia nervosa

https://doi.org/10.1016/0026-0495(92)90198-JGet rights and content

Abstract

The endocrine abnormalities along the growth hormone (GH) axis in anorexia nervosa (AN) and in obesity include hypothalamic, pituitary, and peripheral elements. The present study was undertaken to evaluate the effects of these nutritional extremes on GH-binding protein (BP) levels and on insulin-like growth factor-I (IGF-I) receptors on red blood cells (RBC). Nine patients with AN and 20 obese subjects were compared with normal control children, adolescents, and adults. GH-BP was measured by a binding assay with dextran-coated charcoal separation. IGF-I binding was measured on enriched RBC. Serum GH-BP levels were markedly reduced in the AN patients, and highly increased in the obese. Scatchard analyses showed linear plots with unaltered binding affinities (Ka). The binding capacity (Bmax) was significantly lower than normal control in the AN patients and higher in the obese. GH-BP levels correlated positively with the body mass index (BMI). RBC [125I]IGF-I binding was significantly elevated in the AN patients and low in the obese. Scatchard analyses showed curvilinear plots. The high-affinity constants (Ka1) were slightly, but significantly, higher in the AN patients and in the obese compared with control. The binding capacity of the first binder (Bmax1) was lower in obesity than in AN or control. The low-affinity constants (Ka2) were similar in the three groups, and its binding capacity (Bmax2) was similar in the AN patients and the controls, but significantly lower in the obese. [125I]IGF-I binding correlated negatively and significantly with the BMI and with the GH-BP. AN, with low GH-BP and high IGF-I receptors, can, therefore, be viewed as a condition of GH resistance and IGF-I hypersensitivity. On the other hand, obesity, with high GH-BP and low IGF-I receptors, can be viewed as a condition with GH hypersensitivity and IGF-I resistance. Taken together, these results indicate positive correlation between BMI and GH responsiveness, and negative correlation between BMI and IGF-I responsiveness. The results of the present study show that these two phenomena correlate negatively with each other.

References (60)

  • H Tamai et al.

    Effect of cholinergic muscarinic receptor blockade on growth (GH) releasing hormone-(-1–44)-induced GH secretion in anorexia nervosa

    J Clin Endocrinol Metab

    (1989)
  • RC Casper et al.

    The effect of the nutritional status and weight changes on hypothalamic function tests in anorexia nervosa

  • PO Lundberg et al.

    Effects of thyrotrophin-releasing hormone on plasma levels of TSH, FSH, LH and GH in anorexia nervosa

    Eur J Clin Invest

    (1972)
  • K Maeda et al.

    Growth hormone release following thyrotrophin-releasing hormone injection into patients with anorexia nervosa

    Acta Endocrinol.

    (1976)
  • FF Casanueva et al.

    Growth hormone and prolactin secretion after growth hormone releasing hormone administration in anorexia nervosa patients, normal controls and tamoxifen-pretreated volunteers

    Clin Endocrinol (Oxf)

    (1987)
  • R Rappaport et al.

    Somatomedin activity and growth hormone secretion

    Acta Paediatr Scand

    (1980)
  • MF Ball et al.

    Growth hormone response in the thinned obese

    J Clin Endocrinol Metab

    (1972)
  • G Cinschi et al.

    Effect of arginine on serum levels of insulin and growth hormone in obese subjects

    Metabolism

    (1967)
  • M Fingerhut et al.

    Plasma growth hormone response to l-dopa in obese subjects

    Metabolism

    (1984)
  • T Williams et al.

    Impaired growth hormone responses to growth hormone-releasing factor in obesity

    N Engl J Med

    (1984)
  • AK Dubey et al.

    Metabolic clearance rates of synthetic human growth hormone in lean and obese male rhesus monkeys

    J Clin Endocrinol Metab

    (1988)
  • DW Leung et al.

    Growth hormone receptor and serum binding protein: Purification, cloning and expression

    Nature

    (1987)
  • T Bick et al.

    The interrelationship of growth hormone (GH), liver membrane GH receptor, serum GH-binding protein activity and insulin-like growth factor-I (IGF-I) in the male rat

    Endocrinology

    (1990)
  • WH Daughaday et al.

    Absence of serum growth hormone binding protein in patients with growth hormone receptor deficiency (Laron dwarfism)

  • Z Hochberg et al.

    Alterations of human growth hormone binding by rat liver membranes during hypo- and hyperthyroidism

    Endocrinology

    (1990)
  • Z Hochberg et al.

    The effect of human growth hormone (GH) therapy on GH binding protein in GH deficient children

    Acta Endocrinol

    (1991)
  • T Amit et al.

    Effects of hypo- or hyperthyroidism on growth hormone-binding protein

    Clin Endocrinol

    (1991)
  • T Amit et al.

    A new and convenient assay of growth hormone binding protein activity in human serum

    J Clin Endocrinol Metab

    (1990)
  • N Hizuka et al.

    Characterization of insulin-like growth factor I receptor on human erythrocytes

    J Clin Endocrinol Metab

    (1985)
  • RW Furlaneto et al.

    Estimation of somatomedin-C levels in normal and patients with pituitary disease by radioimmunoassay

    J Clin Invest

    (1977)
  • Cited by (191)

    • Growth hormone and insulin-like growth factor 1 secretions in eating disorders: Correlations with psychopathological aspects of the disorders

      2018, Psychiatry Research
      Citation Excerpt :

      Furthemore, 24 h hormone production and half life are increased, together with normal or increased responses to stimulation with growth hormone-releasing hormone (GHRH), hexarelin, insulin, apomorphine, L-Dopa, clonidine, and to inhibition with glucose or glucagon (Casanueva et al., 1997; Masuda et al. (1988); Kaye et al., 1998; Coiro et al. (1990); Giusti et al. (1997); Gianotti et al., (1998, 1999, 2000); Douyon and Schteingart (2002); Van Neuwpoort and Drent, 2008. whereas concentrations of GH binding protein (GH-BP), insulin-like growth factor-1 (IGF-1), IGF-1 binding protein (IGF-1-BP), the acid-labile subunits of IGF-BP-3 complex, somatostatin, and hormonal response to acetylcholine agonists are all reduced (Counts et al., 1992; Hochberg et al., 1992; Ghigo et al., 1994; Muller and Rolla, 1996; Mancini et al., 1996; Argente et al., 1998; Stoving et al., 1999; Barrios et al., 2001; Gross et al., 2003; Grinspoon et al., 2003). The reduced synthesis and release of IGF-1 result in impairments of the peripheral effects of GH and negative IGF-1 feedback action on GH secretion (Postel Vinay et al., 1995; Scacchi et al., 2005; Paszynska et al., 2015).

    • Growth hormone binding protein - Physiological and analytical aspects

      2015, Best Practice and Research: Clinical Endocrinology and Metabolism
      Citation Excerpt :

      Binding of the placental growth hormone variant (placental GH, GH-V) to the high-affinity GHBP is not different from the binding of pituitary GH [77]. Numerous studies could show a positive correlation between body mass index (BMI) and GHBP levels [68,78–82]. Furthermore, there is a positive correlation of GHBP concentration with (visceral) fat mass, waist circumference, waist-to-hip ratio, insulin secretion, and leptin concentration and a negative correlation with insulin sensitivity and lean body mass [83–85].

    • Obesity, growth hormone and weight loss

      2010, Molecular and Cellular Endocrinology
    • Bioactive insulin-like growth factor-I in obesity

      2009, Journal of Clinical Endocrinology and Metabolism
    View all citing articles on Scopus
    1

    Supported by a grant from the Chief Scientist, Israel Ministry of Health, to M.B.H.Y. and T.A.

    View full text