This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, J.-W. Articles by Frystyk, J. Search for Related Content PubMed PubMed Citation Articles by Chen, J.-W. Articles by Frystyk, J. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Diets Related Collections Neuroendocrinology and Pituitary

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

Medical Research Laboratories and Medical Department M (J.-W.C., J.S.C., H.Ø., J.F.), Aarhus University Hospital, Nørrebrogade, and Laboratory of Biochemical Pathology (J.-W.C.), Aarhus University Hospital, DK-8000 Aarhus C, Denmark; and Diabetes Research Centre (K.H., H.B.-N.), Department of Endocrinology, Odense University Hospital, DK-5000 Odense C, Denmark

Address all correspondence and requests for reprints to: Dr. Jan Frystyk, Medical Research Laboratories and Medical Department M, Aarhus Kommune Hospital, Norrebrogade 44, DK-8000 Aarhus C, Denmark. E-mail: jan{at}frystyk.dk.

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.

This article has been cited by other articles:

				A. Rickenlund, M. Thoren, A. Nybacka, J. Frystyk, and A. Linden Hirschberg Effects of oral contraceptives on diurnal profiles of insulin, insulin-like growth factor binding protein-1, growth hormone and cortisol in endurance athletes with menstrual disturbance Hum. Reprod., October 19, 2009; (2009) dep350v1. [Abstract] [Full Text] [PDF]

				J. D Veldhuis, D. M Keenan, J. N Bailey, J. M Miles, and C. Y Bowers Preservation of GHRH and GH-releasing peptide-2 efficacy in young men with experimentally induced hypogonadism Eur. J. Endocrinol., August 1, 2009; 161(2): 293 - 300. [Abstract] [Full Text] [PDF]

				L. Moller, L. Dalman, H. Norrelund, N. Billestrup, J. Frystyk, N. Moller, and J. O. L. Jorgensen Impact of Fasting on Growth Hormone Signaling and Action in Muscle and Fat J. Clin. Endocrinol. Metab., March 1, 2009; 94(3): 965 - 972. [Abstract] [Full Text] [PDF]

				S. Yakar, C. J. Rosen, M. L. Bouxsein, H. Sun, W. Mejia, Y. Kawashima, Y. Wu, K. Emerton, V. Williams, K. Jepsen, et al. Serum complexes of insulin-like growth factor-1 modulate skeletal integrity and carbohydrate metabolism FASEB J, March 1, 2009; 23(3): 709 - 719. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, D. M. Keenan, J. N. Bailey, A. Adeniji, J. M. Miles, R. Paulo, M. Cosma, and C. Soares-Welch Estradiol Supplementation in Postmenopausal Women Attenuates Suppression of Pulsatile Growth Hormone Secretion by Recombinant Human Insulin-like Growth Factor Type I J. Clin. Endocrinol. Metab., November 1, 2008; 93(11): 4471 - 4478. [Abstract] [Full Text] [PDF]

				J. L. Chan, C. J. Williams, P. Raciti, J. Blakeman, T. Kelesidis, I. Kelesidis, M. L. Johnson, M. O. Thorner, and C. S. Mantzoros Leptin Does Not Mediate Short-Term Fasting-Induced Changes in Growth Hormone Pulsatility but Increases IGF-I in Leptin Deficiency States J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2819 - 2827. [Abstract] [Full Text] [PDF]

				J. Frystyk, R. A. Ritzel, J. Maubach, M. Busing, R. Luck, J. Klempnauer, W. Schmiegel, and M. A. Nauck Comparison of Pancreas-Transplanted Type 1 Diabetic Patients with Portal-Venous Versus Systemic-Venous Graft Drainage: Impact on Glucose Regulatory Hormones and the Growth Hormone/Insulin-Like Growth Factor-I Axis J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1758 - 1766. [Abstract] [Full Text] [PDF]

				K. C. Lasseter, L. Shaughnessy, D. Cummings, J. C. Pezzullo, W. Wargin, R. Gagnon, J. Oliva, and G. Kosutic Ghrelin Agonist (TZP-101): Safety, Pharmacokinetics and Pharmacodynamic Evaluation in Healthy Volunteers: A Phase I, First-in-Human Study J. Clin. Pharmacol., February 1, 2008; 48(2): 193 - 202. [Abstract] [Full Text] [PDF]

				J. Leger, I. Mercat, C. Alberti, D. Chevenne, P. Armoogum, J. Tichet, and P. Czernichow The relationship between the GH/IGF-I axis and serum markers of bone turnover metabolism in healthy children Eur. J. Endocrinol., November 1, 2007; 157(5): 685 - 692. [Abstract] [Full Text] [PDF]

				A. Vrieling, D. W Voskuil, J. M Bonfrer, C. M Korse, J. van Doorn, A. Cats, A. C Depla, R. Timmer, B. J Witteman, F. E van Leeuwen, et al. Lycopene supplementation elevates circulating insulin-like growth factor binding protein-1 and -2 concentrations in persons at greater risk of colorectal cancer Am. J. Clinical Nutrition, November 1, 2007; 86(5): 1456 - 1462. [Abstract] [Full Text] [PDF]

				E. Capoluongo, F. Ameglio, P. Lulli, A. Minucci, C. Santonocito, P. Concolino, E. Di Stasio, S. Boccacci, V. Vendettuoli, G. Giuratrabocchetta, et al. Epithelial lining fluid free IGF-I-to-PAPP-A ratio is associated with bronchopulmonary dysplasia in preterm infants Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E308 - E313. [Abstract] [Full Text] [PDF]

				G. Onder, R. Liperoti, A. Russo, M. Soldato, E. Capoluongo, S. Volpato, M. Cesari, F. Ameglio, R. Bernabei, and F. Landi Body mass index, free insulin-like growth factor I, and physical function among older adults: results from the ilSIRENTE study Am J Physiol Endocrinol Metab, October 1, 2006; 291(4): E829 - E834. [Abstract] [Full Text] [PDF]

				J.-W. Chen, M. F Nielsen, A. Caumo, H. Vilstrup, J. S. Christiansen, and J. Frystyk Changes in bioactive IGF-I and IGF-binding protein-1 during an oral glucose tolerance test in patients with liver cirrhosis. Eur. J. Endocrinol., August 1, 2006; 155(2): 285 - 292. [Abstract] [Full Text] [PDF]

				D. L. Hadsell, D. T. Torres, N. A. Lawrence, J. George, A. F. Parlow, A. V. Lee, and M. L. Fiorotto Overexpression of Des(1-3) Insulin-Like Growth Factor 1 in the Mammary Glands of Transgenic Mice Delays the Loss of Milk Production with Prolonged Lactation Biol Reprod, December 1, 2005; 73(6): 1116 - 1125. [Abstract] [Full Text] [PDF]

				K. Stokes, M. Nevill, J. Frystyk, H. Lakomy, and G. Hall Human growth hormone responses to repeated bouts of sprint exercise with different recovery periods between bouts J Appl Physiol, October 1, 2005; 99(4): 1254 - 1261. [Abstract] [Full Text] [PDF]