Role of pulsatile growth hormone (GH) secretion in the regulation of lipolysis in fasting humans

BACKGROUND: The increase in growth hormone (GH) secretion during a prolonged fast stimulates lipolytic rate, thereby augmenting the mobilization of endogenous energy at a time when fuel availability is very low. STUDY AIM: To identify the specific component of GH secretory pattern responsible for the stimulation of lipolytic rate during fasting in humans. STUDY PROTOCOL: We measured lipolytic rate (using stable isotope dilution technique) after an overnight fast in 15 young, healthy, non-obese subjects (11 men and 4 women), and again on four separate occasions after a 59 h fast. These four prolonged fasting trials differed only by the contents of an infusion solution provided throughout the 59 h fasting period. Subjects were infused either with normal saline (“Control”; n = 15) or with graded doses of a GH Releasing Hormone Receptor Antagonist (GHRHa):10 μg/kg/h (“High”; n = 15), 1 μg /kg/h (“Medium”; n = 8), or 0.5 μg /kg/h (“Low”; n = 6). RESULTS: As expected, the 59 h fast completely suppressed plasma insulin levels and markedly increased endogenous GH concentrations (12 h vs 59 h Fast; p = 0.0044). Administration of GHRHa induced dose-dependent reduction in GH concentrations in response to the 59 h fast (p < 0.05). We found a strong correlation between the rate of lipolysis and GH mean peak amplitude (R = 0.471; p = 0.0019), and total GH pulse area under the curve (AUC) (R = 0.49; p = 0.0015), but not the GH peak frequency (R = 0.044; p = 0.8) or interpulse GH concentrations (R = 0.25; p = 0.115). CONCLUSION: During prolonged fasting (i.e., 2–3 days), when insulin secretion is abolished, the pulsatile component of GH secretion becomes a key metabolic regulator of the increase in lipolytic rate.