Free Rather than Total Circulating Insulin-Like Growth Factor-I Determines the Feedback on Growth Hormone Release in Normal Subjects

• Published in: The journal of clinical endocrinology and metabolism Vol. 90; no. 1; pp. 366 - 371
• Main Authors: Chen, Jian-Wen, Højlund, Kurt, Beck-Nielsen, Henning, Sandahl Christiansen, Jens, Ørskov, Hans, Frystyk, Jan
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01-01-2005; Copyright by The Endocrine Society
• Subjects: Adult; Biological and medical sciences; Endocrinopathies; Fasting - metabolism; Fatty Acids, Nonesterified - blood; Feedback; Female; Fundamental and applied biological sciences. Psychology; Human Growth Hormone - secretion; Humans; Insulin-Like Growth Factor Binding Proteins - blood; Insulin-Like Growth Factor I - analysis; Male; Medical sciences; Vertebrates: endocrinology; Human; Adenohypophyseal hormone; Hormonal regulation; Somatotropin hormone; Insulin like growth factor 1; Endocrinology; Release
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2004-0039

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/m2) 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 μg/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 μg/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.