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Metabolic Effects and Pharmacokinetics of a Growth Hormone Pulse in Healthy Adults: Relation to Age, Sex, and Body Composition

Medical Department M (Endocrinology and Diabetes) and Center for Clinical Pharmacology, Aarhus University Hospital, Kommunehospitalet, Aarhus, Denmark

Address all correspondence and requests for reprints to: Nina Vahl, M.D., Medical Department M, Aarhus Kommunehospital, DK-8000 C Aarhus, Denmark.

The acute effects of a single GH pulse have previously been studied in young males. It is, however, likely that both the metabolic effects and the pharmacokinetics of GH may differ between age groups and sexes. We studied 36 healthy, clinically nonobese adults of both sexes, who were divided into a young group (mean age, 29.6 yr) and an older group (mean age, 51.0 yr). On 2 separate occasions, they received an iv bolus of either GH (200 µg) or saline followed by blood sampling for 5 h. Glucose turnover was estimated by infusion of [3-³H]glucose, and indirect calorimetry was performed before and 2 h after the bolus infusions. Body composition (computed tomography scan and dual energy x-ray absorptiometry) was performed at baseline. Baseline levels of serum insulin-like growth factor I (IGF-I) was lower in older subjects, whereas circulating IGF-binding protein-1 and lipid intermediates were lower in males than in females. The area under the GH curve was lower in older subjects (young, 3978 ± 1532 µg/L·24 h; older, 1144 ± 79; P = 0.001), whereas the elimination half-life did not differ with age (young, 18.1 ± 0.9 min; older, 16.4 ± 0.8; P = NS). The MCR and apparent distribution volume of GH were higher in older subjects [MCR: young, 0.11 ± 0.02 min/L; older, 0.19 ± 0.01; P = 0.001; apparent distribution volume: young, 2.5 ± 0.4 L; older, 4.5 ± 0.3; P < 0.001). Both MCR and V_d correlated inversely with age and positively with indexes of adiposity. GH significantly increased lipid intermediates, but the response was higher in young subjects and males. By contrast, the ability of GH to acutely suppress IGF-binding protein-1 was more pronounced in older subjects and females. Serum levels of insulin and IGF-I did not differ significantly between GH and saline treatment groups. GH decreased the respiratory exchange ratio and increased resting energy expenditure, with no age or gender differences. A gradual decline over time in plasma levels and rate of turnover of glucose was recorded after both GH and saline. The following conclusions were reached. 1) The MCR and V_d of GH increase with age and correlate positively with fat mass. 2) Older subjects are responsive to the acute lipolytic effects of GH, but the response is higher in young subjects and in males. 3) Adipose tissue may be actively involved in the distribution and clearance of GH. 4) Age, sex, and body composition interact with GH in a complex manner, involving clearance, distribution, and metabolic actions of the hormone.

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