Joint mechanisms of impaired growth-hormone pulse renewal in aging men

Context: Aging reduces the size (mass) of GH secretory bursts and thereby reduces total GH secretion. Experimental data indicate that high-amplitude GH pulses are evoked by reversible cycles of GHinduced negative feedback. Whether aging impairs autofeedback is unknown. Objective: The objective of this study is to assess whether age attenuates and IGF-I potentiates negative feedback by a near-physiological pulse of GH. Design/Setting/Subjects: In a university setting, 17 healthy men ages 19-71 yr each underwent four randomly ordered infusion studies on separate mornings fasting. Intervention: Intravenous injection of a pulse of: 1) saline or 2) recombinant human (rh) GH to impose controlled negative feedback, followed in 2 h by a bolus of 3) saline or (iv) the ghrelin analog GHRP-2 to overcome feedback inhibition. Outcome Measures: The impact of age and IGF-I concentrations on GH autofeedback was assessed by regression analysis. Results: Percentage feedback inhibition correlated negatively with: 1) age after consecutive rh GH/saline infusion (R₂ = 0.42, P = 0.005) at any IGF-I concentration; and 2) total IGF-I concentrations after rh GH/GHRP-2 infusion (R₂ = 0.40, P = 0.009) at any age. In contrast, sex-steroid concentrations and body mass index were unrelated to degree of autoinhibition. Conclusions: Increased age in healthy men predicts impaired GH autofeedback, which may contribute to attenuated renewal of highamplitude GH pulses. Conversely, higher IGF-I concentrations in young men forecast accentuated GH autoinhibition, which may drive prominent GH pulses.