Relationship between growth hormone (GH) status, serum leptin and body composition in healthy and GH deficient elderly subjects

OBJECTIVE: Growth hormone (GH) secretion declines with age and is affected by body composition. The signal that mediates the latter relationship remains ill-defined. Leptin, the protein product of the adipocyte specific ob gene, is thought to accurately reflect fat mass and could therefore be a candidate to influence GH secretion. We have therefore investigated the relationship between GH status, leptin and body composition in normal and GH-deficient elderly subjects. DESIGN: GH secretion was assessed by 20-minute sampling over 24 hours and serum leptin concentrations were measured in a single morning, fasted sample. PATIENTS: Twenty-one GH deficient elderly patients (61-83 years) and 22 gender- and BMI-matched controls (61-88 years). MEASUREMENTS: Body composition was assessed by dual- energy X-ray absorptiometry (DEXA). GH was measured in an ultrasensitive chemiluminescent assay and serum leptin was determined by radioimmunoassay. RESULTS: Leptin was correlated with percentage body fat in both sexes (male r=0.75, female r=0.89, both P<0.001). Male patients had increased fat mass (FM) (P<0.01) and leptin concentrations (P<0.05) but similar lean mass (LM) compared with controls. However, leptin concentration per unit FM was identical in both groups (P=0.3). In contrast, female patients had lower LM (P<0.05) but similar FM to controls, yet their leptin concentration per unit FM was twice that of the controls (P<0.05). In multiple linear regression (MLR) leptin was determined positively by FM and negatively by LM (controls r² = 76%; patients r²=73%, both P<0.0001). When controlled for gender, GH secretion in the controls was correlated negatively with leptin (r=-0.68, P<0.01) and negatively with percentage body fat (r=-0.73, P<0.01). In MLR, using leptin as a marker of body composition, 66% of the variability in GH secretion in the controls could be explained by gender (38%) and by leptin (28%). CONCLUSIONS: Both decreased lean mass and increased fat mass raise serum leptin concentrations in normal and growth hormone-deficient elderly subjects. Leptin is therefore a marker of body composition rather than fat mass alone. The influence of body composition on growth hormone secretion in the elderly may be mediated through leptin, acting as a peripheral signal from adipose tissue to decrease GH secretion.