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Joint Mechanisms of Impaired Growth-Hormone Pulse Renewal in Aging Men

Endocrine Research Unit Department of Internal Medicine (J.D.V.), Mayo School of Graduate Medical Education, Mayo Clinic, Rochester, Minnesota 55905; Endocrine Service (A.I.), Research and Development, Salem Veterans Affairs Medical Center, Salem, Virginia 24153; and Division of Endocrinology and Metabolism (C.Y.B.), Department of Internal Medicine, Tulane University Medical Center, New Orleans, Louisiana 70112-2699

Address all correspondence and requests for reprints to: Johannes D. Veldhuis, Endocrine Research Unit, Department of Internal Medicine, Mayo School of Graduate Medical Education, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota 55905. E-mail: veldhuis.johannes{at}mayo.edu.

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 GH-induced 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 high-amplitude GH pulses. Conversely, higher IGF-I concentrations in young men forecast accentuated GH autoinhibition, which may drive prominent GH pulses.

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