Effects of Growth Hormone (GH) on Ghrelin, Leptin, and Adiponectin in GH-Deficient Patients

Ghrelin is an endogenous ligand specific for the growth hormone (GH) secretagogue receptor and is the most potent known substance releasing GH. It also increases appetite, glucose oxidation, and lipogenesis. GH, in contrast, promotes lipolysis and glucose production. Taking nutrients, especially glucose, depresses levels of both ghrelin and GH. Leptin and adiponectin are peptides whose levels correlate with adipose tissue mass. Serum leptin levels reportedly are increased in patients with GH deficiency (GHD). This study was done to determine the effects of GH treatment on levels of these substances in 36 patients known to have GHD for just over 10 years on average. All but 2 patients had complete pituitary insufficiency. Patients were randomized to receive either GH or placebo for 9 months and, after a 3-month washout period, the other treatment for 9 months longer. Recombinant human GH was begun in a dose of 0.5 U/m2 and the dose was increased as needed up to a maximum of 2 U/m2. GH treatment lowered total body fat while increasing fat-free mass. Men lost a small amount of body weight but had no change in body mass index. Levels of both ghrelin and leptin (Fig. 1) declined in men and women. Adiponectin increased in women only (Fig. 2). Estrogen replacement therapy did not alter the findings. Blood glucose levels increased in men given GH, whereas insulin-like growth factor-I (IGF-I) and insulin levels increased in both men and women after GH treatment. The drop in ghrelin correlated directly with decreased body fat and leptin levels, and inversely with the elevation of fat-free mass. Leptin levels correlated strongly with total body fat and inversely with fat-free mass before and after GH treatment. The reductions in leptin and total body fat correlated positively with one another. Insulin levels correlated positively with leptin levels after GH therapy. Levels of adiponectin correlated with body fat after GH. The changes in IGF-1 and fat mass significantly predicted the reduction in ghrelin. Suppression of ghrelin could promote the loss of body fat in patients with GHD who receive GH treatment. Possibly, the GH/IGF-I axis has a negative feedback effect on ghrelin secretion.Fig. 1: Leptin levels (ng/mL ± standard error of mean) before and after 9 months of growth hormone therapy in 21 men and 15 women with growth hormone deficiency. *P < 0.05; ***P < 0.001 versus baseline. Reproduced with permission. J Clin Endocrinol Metab 2003;88:5193–5198. Copyright © 2003, Endocrine Society. All rights reserved.Fig. 2: Adiponectin levels mg/L ± standard error of mean before and after 9 months of growth hormone therapy in 21 men and 15 women with GHD. *P < 0.05 versus baseline. Reproduced with permission. J Clin Endocrinol Metab 2003;88:5193–5198.