Pulsatile growth hormone secretion in normal-weight and obese men: Differential metabolic regulation during energy restriction

Abstract

Metabolic changes such as obesity and fasting modulate pulsatile growth hormone (GH) release in man, but the underlying mechanisms are still elusive. We studied the temporal pattern of pulsatile GH release in five normal-weight men (mean ± SD: age, 29.8 ± 4.9 years; body mass index [BMI], 24.3 ± 1.8 kg/m 2) and five obese men (age, 27.8 ± 4.8 years; BMI, 38.9 ± 4.8 kg/m 2) during their regular energy consumption and the last 24 hours of a 96-hour fasting period. GH plasma levels were determined at 10-minute intervals and glucose level was measured every 20 minutes. GH pulse analysis was performed with three different algorithms. Insulin-like growth factor-I (IGF-I), IGF-II, IGF-binding proteins (IGFBP-1, -2, and -3), and IGF-binding capacity (IGF-BC) were evaluated in samples collected at 7:00 am, 3:00 pm, and 11:00 pm. Twenty-four-hour mean GH was basally higher in normal subjects (1.1 ± 0.6 mU/L) than in overweight subjects (0.4 ± 0.2, P <.01 v normal). The significant fasting-induced GH increase in normal-weight men (to 5.6 ± 2.2 mU/L, P <.05 v basal) was inversely related to BMI ( r = −.86, P = .0006). GH pulse amplitudes but not frequencies were different for both groups and were increased by fasting in normal subjects but not in obese subjects. Plasma glucose showed comparable mean levels basally, and fasting induced a more pronounced decrease of mean glucose in normal men (−1.9 ± 0.6 v −1.4 ± 0.3 mmol/L in obese) with a negative correlation between changes in mean GH and glucose ( r = −.70, P = .022). IGF-I concentrations were similar in both groups and were unchanged with energy restriction, whereas IGF-II showed higher basal and fasting-associated values in obese subjects. The IGF-BC increased significantly during fasting in normal-weight men. In conclusion, nutritional regulation of GH release is associated with a modulation of GH pulse amplitudes, whereas GH pulse frequencies remain unchanged. These results suggest a stable pulse generation with amplitude modifications by direct substrate actions and/or metabolic influences of the somatostatinergic tone. Variations of free IGF-I and IGF-II are involved in the differential GH regulation of lean and obese subjects in periods of regular food intake. During short-term fasting, somatotrope GH release may also be influenced by changes in plasma glucose levels.