Insulin-like growth factor I (IGF-I) exerts a negative feedback effect on GH secretion via either direct actions at the pituitary level or indirect ones at the hypothalamic level, through stimulation of somatostatin (SS) and/or inhibition of GHRH release. In fact, recombinant human IGF-I (rhIGF-I) in humans inhibits spontaneous GH secretion as well as the GH response to GHRH and even more to GH/GH-releasing peptides, whose main action is on the hypothalamus, antagonizing SS and enhancing GHRH

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... tivity. The aim of the present study was to further clarify in humans the mechanisms underlying IGF-I-induced inhibition of somatotroph secretion. In six normal young volunteers (all women; mean Ϯ SEM: age, 28.3 Ϯ 1.2 yr; body mass index, 21.3 Ϯ 1.2 kg/m 2 ) we studied the GH response to GHRH (1 g/kg, iv, at 0 min), both alone and combined with arginine (ARG; 0.5 g/kg, iv, from 0 -30 min), which probably acts via inhibition of hypothalamic SS release, after pretreatment with rhIGF-I (20 g/kg, sc, at Ϫ180 min) or placebo. rhIGF-I increased circulating