Journal of Clinical Endocrinology & Metabolism, Vol 72, 582-587, Copyright © 1991 by Endocrine Society

ARTICLES

Short-term changes in serum insulin-like growth factors (IGF) and IGF binding protein 3 after different modes of intravenous growth hormone (GH) exposure in GH-deficient patients

JO Jorgensen, WF Blum, N Moller, MB Ranke and JS Christiansen
Second University Clinic of Internal Medicine, Aarhus Kommunehospital, Denmark.

Virtually all circulating insulin-like growth factors I and II (IGF-I and IGF-II) are bound to specific binding proteins (IGFBP), of which IGFBP-3 is the quantitatively most important. The mechanisms regulating the close coordination between serum levels of IGFs and IGFBP-3 is poorly understood. We therefore evaluated the temporal association of serum IGF-I, IGF-II, and IGFBP-3 measured by RIAs after well defined short-term GH exposure in GH-deficient patients. Six patients (mean +/- SE age: 20.5 +/- 1.1 yr) each underwent three GH study protocols in random order. Each study was preceded by 4 weeks without GH therapy. Two units of GH were administered iv as either: 1) two boluses, 2) eight boluses, or 3) a constant infusion. The duration of each study was 44 h including at least 16 h after termination of GH administration. Increments in serum IGF-I occurred 4-6 h after initiated GH exposure in all studies. In the two-bolus study the IGF-I increase was modest with mean +/- SE peak values of 12.4 +/- 2.1 nmol x L-1 after GH administration. In the eight bolus and constant infusion studies significantly higher IGF-I levels were generated: 17.0 +/- 2.2 nmol x L-1 (8 bolus) and 18.8 +/- 1.1 h nmol x L-1 (infusion). In contrast the time course change in serum IGF-II did not differ in the three studies, and it was characterised by a sluggish increase of approximately 30% evidenced after 16-20 h. The changes in IGFBP-3 were almost identical in the three studies. After a lag phase of approximately 18-20 h a gradual increase of approximately 40%, which had not ceased at the end of the study period, was observed. The molar ratio of serum IGF-I plus IGF-II:serum IGFBP-3 remained constant with values between 0.8-0.9 except in the constant infusion experiment, in which the ratio increased significantly with time reaching a mean peak value, which exceeded 1.0, after 24 h. Our data suggest that a pulsatile GH pattern is not superior to constant GH levels as regards generation of IGFs and IGFBP. The earlier increase in serum IGF-I compared to IGF-II and IGFBP-3 suggests that IGF-I may be the main regulator of IGFBP-3 production. Accordingly, the slow increase in serum IGF-II, which paralleled that of IGFBP-3, could indicate that serum IGF-II levels mainly depend on the concentration or binding site availability of IGFBP-3.

This article has been cited by other articles:

				T. Munzer, C. J. Rosen, S.M. Harman, K. M. Pabst, C. St. Clair, J. D. Sorkin, and M. R. Blackman Effects of GH and/or sex steroids on circulating IGF-I and IGFBPs in healthy, aged women and men Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E1006 - E1013. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, J. N. Roemmich, E. J. Richmond, and C. Y. Bowers Somatotropic and Gonadotropic Axes Linkages in Infancy, Childhood, and the Puberty-Adult Transition Endocr. Rev., April 1, 2006; 27(2): 101 - 140. [Abstract] [Full Text] [PDF]

				S. K. Jessup, E. V. Dimaraki, K. V. Symons, and A. L. Barkan Sexual Dimorphism of Growth Hormone (GH) Regulation in Humans: Endogenous GH-Releasing Hormone Maintains Basal GH in Women But Not in Men J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4776 - 4780. [Abstract] [Full Text] [PDF]

				C. A. Jaffe, D. K. Turgeon, K. Lown, R. Demott-Friberg, and P. B. Watkins Growth hormone secretion pattern is an independent regulator of growth hormone actions in humans Am J Physiol Endocrinol Metab, November 1, 2002; 283(5): E1008 - E1015. [Abstract] [Full Text] [PDF]

				M. S. Gill, A. A. Toogood, J. Jones, P. E. Clayton, and S. M. Shalet Serum Leptin Response to the Acute and Chronic Administration of Growth Hormone (GH) to Elderly Subjects with GH Deficiency J. Clin. Endocrinol. Metab., April 1, 1999; 84(4): 1288 - 1295. [Abstract] [Full Text]

				S. Rajaram, D. J. Baylink, and S. Mohan Insulin-Like Growth Factor-Binding Proteins in Serum and Other Biological Fluids: Regulation and Functions Endocr. Rev., December 1, 1997; 18(6): 801 - 831. [Abstract] [Full Text]

				Y. J. H. Janssen, M. Frolich, and F. Roelfsema A Low Starting Dose of Genotropin in Growth Hormone-Deficient Adults J. Clin. Endocrinol. Metab., January 1, 1997; 82(1): 129 - 135. [Abstract] [Full Text] [PDF]

				M. Thoren, A. Hilding, R. C. Baxter, M. Degerblad, I.-L. Wivall-Helleryd, and K. Hall Serum Insulin-Like Growth Factor I (IGF-I), IGF-Binding Protein-1 and -3, and the Acid-Labile Subunit as Serum Markers of Body Composition during Growth Hormone (GH) Therapy in Adults with GH Deficiency J. Clin. Endocrinol. Metab., January 1, 1997; 82(1): 223 - 228. [Abstract] [Full Text] [PDF]