Adaptation of ghrelin and the GH/IGF axis to high altitude

Abstract

High altitude (HA) provokes a variety of endocrine adaptive processes. We investigated the impact of HA on ghrelin levels and the GH/IGF axis. Observational study as part of a medical multidisciplinary project in a mountainous environment. Thirty-three probands (12 females) were investigated at three timepoints during ascent to HA (A: d -42, 120 m; B: d +4, 3440 m; C: d +14, 5050 m). The following parameters were obtained: ghrelin; GH; GH-binding protein (GHBP); IGF1; IGF2; IGF-binding proteins (IGFBPs) -1, -2, and -3; acid-labile subunit (ALS); and insulin. Weight was monitored and general well being assessed using the Lake Louise acute mountain sickness (AMS) score. Ghrelin (150 VS 111PG/ML; P0.01) and GH (3.4 VS 1.7G/L; P0.01) were significantly higher at timepoint C compared with A whereas GHBP, IGF1, IGF2, IGFBP3, ALS, and insulin levels did not change. IGFBP1 (58 VS 47G/L; P0.05) and, even more pronounced, IGFBP2 (1141 VS 615G/L; P0.001) increased significantly. No correlation, neither sex-specific nor in the total group, between individual weight loss (females: -2.1 kg; males: -5.1 kg) and rise in ghrelin was found. Five of the subjects did not reach investigation point C due to AMS. After 14 days of exposure to HA, we observed a significant ghrelin and GH increase without changes in GHBP, IGF1, IGF2, IGFBP3, ALS, and insulin. Higher GH seems to be needed for acute metabolic effects rather than IGF/IGFBP3 generation. Increased IGFBP1 and -2 may reflect effects from HA on IGF bioavailability.