title: Free rather than total circulating insulin-like growth factor-I determines the feedback on growth hormone release in normal subjects.
abstract: Pituitary GH secretion is feedback regulated by circulating IGF-I. However, it remains to be determined whether the feedback control is mediated through circulating free or total IGF-I. To study this, we compared the temporal changes in circulating levels of GH vs. free and total IGF-I during fasting. Seventeen healthy normal-weight subjects (body mass index 23.4 +/- 0.6 kg/m(2)) were studied during 80 h of fasting. Serum was assayed for GH every 3 h; total, free, and bioactive IGF-I, IGF binding protein (IGFBP)-1, -2, and -3 as well as IGFBP-1 bound IGF-I were assayed every morning. During fasting, mean 24-h GH levels increased from 1.41 +/- 0.20 to 3.01 +/- 0.46 and 2.09 +/- 0.30 microg/liter (d 1 vs. d 2 and 3; P < 0.03). After 24 h of fasting, free and bioactive IGF-I had decreased by 40 +/- 5 and 17 +/- 5%, respectively (P < 0.02), and both concentrations remained suppressed for the rest of the study. In contrast, total IGF-I remained unchanged until the end of d 3, at which levels were slightly reduced (P < 0.007). IGFBP-1 increased from 38 +/- 2 to 137 +/- 24, 212 +/- 32, and 214 +/- 22 microg/liter (d 1 vs. d 2, d 3, and end of d 3; P < 0.0001), and these changes closely paralleled those of IGFBP-1-bound IGF-I (P < 0.0001). IGFBP-2 increased only transiently at d 2 (P < 0.05), and IGFBP-3 remained unchanged. The increase in mean 24-h GH levels from d 1 to d 2 correlated inversely with the relative reduction in free IGF-I from d 1 to d 2 (r = -0.51; P = 0.04), i.e. the larger the reduction in free IGF-I, the larger the increase in GH. None of the other IGF-related parameters correlated with GH. In conclusion, the temporal relationship between the increase in GH and the reduction in free IGF-I supports the hypothesis that circulating free IGF-I mediates the feedback regulation of GH secretion.
authors.affiliation: Medical Research Laboratories and Medical Department M, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus C, Denmark.
authors.forename: Jian-Wen
authors.initials: JW
authors.lastname: Chen
authors.forename: Kurt
authors.initials: K
authors.lastname: Højlund
authors.forename: Henning
authors.initials: H
authors.lastname: Beck-Nielsen
authors.forename: Jens
authors.initials: J
authors.lastname: Sandahl Christiansen
authors.forename: Hans
authors.initials: H
authors.lastname: Orskov
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
mesh_terms: D000328:Adult; D005215:Fasting / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005246:Feedback; D005260:Female; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male
chemical_list: D005230:Fatty Acids, Nonesterified; D018969:Insulin-Like Growth Factor Binding Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I