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The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 11 4310-4314
Copyright © 2000 by The Endocrine Society

Original Studies

Stimulation of the 150-Kilodalton Insulin-Like Growth Factor-Binding Protein-3 Ternary Complex by Continuous and Pulsatile Patterns of Growth Hormone (GH) Administration in GH-Deficient Patients1

Torben Laursen, Allan Flyvbjerg, Jens O. L. Jørgensen, Robert C. Baxter and Jens S. Christiansen

Center for Clinical Pharmacology, Department of Pharmacology, Aarhus University (T.L.), and Medical Department M (Diabetes and Endocrinology), Aarhus University Hospital, Kommunehospitalet (A.F., J.O.L.J., J.S.C.), DK-8000 Aarhus C, Denmark; and Kolling Institute of Medical Research, Royal North Shore Hospital (R.C.B.), St. Leonards, New South Wales 2065, Australia

Address all correspondence and requests for reprints to: Dr. Torben Laursen, Ph.D., Center for Clinical Pharmacology, Department of Pharmacology, Aarhus University, Bartholin Building, DK-8000 Aarhus C, Denmark. E-mail: tl{at}farm.au.dk/torben.laursen@dadlnet.dk


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
In the circulation insulin-like growth factor I (IGF-I), IGF-binding protein 3 (IGFBP-3), and the acid-labile subunit (ALS) form a 150-kDa ternary complex that is of importance for the regulation of IGF-I bioactivity. GH administration is known to increase each of the single components of the ternary complex, and in GH-deficient rats formation of the 150-kDa complex is induced more by continuous than by pulsatile GH patterns. The aim of the present studies was to study the effects of the GH administration pattern on the formation of the 150-kDa ternary complex in humans. A fixed total GH dose (2 IU/m2·24 h) was administered iv randomly as 1) continuous infusion or 2) eight bolus injections to five GH-deficient patients over a period of 24 h. GH administration significantly increased serum IGF-I and IGFBP-3 levels and the IGF-I/IGFBP-3 ratio. IGF-I levels increased most pronouncedly after continuous administration (P < 0.01). Serum ALS levels increased significantly (both P < 0.005) from 94 ± 21 to 180 ± 29 (infusion) and from 85 ± 17 to 155 ± 17 nmol/L (pulses). Employment of neutral size exclusion chromatography enabled separation of IGFBP-3 in ternary complex and noncomplex-bound fractions. IGFBP-3 in the ternary complex increased significantly after GH administration [by 44% (P = 0.048) during infusion and by 62% (P = 0.004) during bolus]. The noncomplex-associated IGFBP-3 fraction, however, did not increase significantly after GH administration (P = NS). Finally, formation of the ternary complex was unaffected by the pattern of GH delivery. In conclusion, short-term GH administration increased all components of the 150-kDa ternary complex. Higher levels of IGF-I after constant GH exposure could indicate an increased bound fraction. However, the GH pattern did not influence the induction of the ternary complex itself. Continuous and intermittent GH patterns may be clinically equally effective during long-term GH therapy, as judged by levels of the components of the ternary complex.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
CIRCULATING LEVELS of insulin-like growth factor I (IGF-I) are associated with at least six IGF-binding proteins (IGFBP), of which IGFBP-3 binds 90–95% of the circulating IGF-I. Levels of IGF-I and IGFBP-3 are low in GH deficiency. GH administration increases circulating concentrations of IGF-I, IGFBP-3, and the acid-labile subunit (ALS). By interaction with ALS (1), IGF-I and IGFBP-3 have been shown to form a stable 150-kDa ternary complex in rats and humans (2, 3). The complex serves as a reservoir of IGF-I and regulates IGF-I bioavailability to tissues by protecting it against degradation, resulting in an extended half-life of the growth factor (4). In experimental conditions incubation of purified ALS with iodinated IGF-I and recombinant IGFBP-3 increases the amount of bound IGF-I (5). Other studies, however, have shown that ALS stimulates IGF binding to proteolysed (6), but not intact, glycosylated IGFBP-3 (7).

Although the endogenous pattern of GH secretion is pulsatile, a study in GH-deficient (GHD) rats reported that the ternary complex is induced more effectively by continuous than by pulsatile GH administration (8). However, discrepant effects of pulsatile and continuous GH exposure have been reported in rodents and humans. In rats, IGF-I levels were increased more by pulsatile GH patterns (9), whereas continuous delivery was similarly effective in humans (10). GH-binding protein (GHBP) and GH receptor were up-regulated by continuous GH exposure in rats (11), whereas pulsatile and continuous GH patterns resulted in similar GHBP levels in humans (12).

In the present study the impact of GH on formation of the ternary complex and its individual components was studied in GHD patients. Furthermore, the role of the GH administration pattern in complex formation has been examined.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects

Five GHD patients were studied. The diagnosis was defined by a peak GH response of less than 5 µg/L after two different stimulation tests (insulin-induced hypoglycemia, arginine infusion, or heat exposure). Most of the patients suffered from additional pituitary insufficiencies. It was documented within close proximity to the study protocol that they received adequate replacement therapy with hydrocortisone, T4, and sex steroids. The characteristics of the patients are shown in Table 1Go. Mean age was 39 yr (range, 20–50.), and mean body mass index (body weight/height2) was 29.0 kg/m2.


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  		Table 1. Patient characteristics

 
Experimental protocol

Among samples from a previous study (13), sera from five patients were randomly chosen to examine the effects of GH on ternary complex formation. After withdrawal of GH replacement therapy for 4 weeks, the patients were followed on two different occasions for 36 h. The two studies were separated by a 4-week wash-out period. Blood samples were drawn at baseline in the GH-depleted state and after 36 h, when the circulating GH concentrations had returned to baseline levels not significantly different from zero in both situations (13). In a randomized cross-over design a fixed GH dose (2 IU/m2·24 h) was administered iv during the initial 24 h of the study as 1) continuous infusion or 2) eight identical doses injected every 3.5 h. The infusion was performed by means of an infusion pump (Harvard Apparatus, Inc., Natick, MA).

The study protocol was approved by the Danish health authorities and the regional ethics committee and was conducted in accordance with Helsinki Declaration II.

Analyses

Serum IGF-I were measured by noncompetitive time-resolved immunofluorometric assays (14), with a lower detection limit of less than 2.5 ng/L. Serum levels of ALS were measured by a RIA as previously described (15), and serum IGFBP-3 was measured by a commercial immunoradiometric assay kit (Diagnostics Systems Laboratories, Inc., Webster, TX). The intra- and interassay coefficients of variation (CVs) for the assays used were less than 5% and 10%, respectively. To determine the distribution of IGFBP-3 in the 150-kDa ternary complex and the nonternary complex bound fraction, 0.2 mL serum was exposed to neutral size exclusion chromatography as previously described (8) followed by determination of the IGFBP profile by Western ligand blotting (16), and finally measurement of the IGFBP-3 concentration by an immunoradiometric assay, as described above. The column used for neutral size exclusion chromatography was equilibrated with the gel filtration standards thyroglobulin (670 kDa), {gamma}-globulin (158 kDa), ovalbumin (44 kDa), myoglobin (17 kDa), and cyanocobalamin (1.4 kDa; all from Bio-Rad Laboratories, Inc., Melville, NY). Blood samples were stored at -20 C.

Statistics

The results are given as the mean ± SEM. Comparisons were performed by paired Student’s t test. The calculations were performed on normally distributed or logarithmic transformed data, or alternatively nonparametric statistics were employed. P < 0.05 was considered significant.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
GH administration induced significant increase in serum levels of IGF-I (P < 0.01) and IGFBP-3 (P < 0.005). A significantly higher increment in serum IGF-I levels (Fig. 1Go, upper panel) was achieved after continuous infusion compared with pulses (P < 0.01). The increase in serum IGFBP-3 (Fig. 1Go, middle panel) levels, however, was not statistically significantly different between the two different modes of short-term GH delivery (P = 0.10). GH administration also increased (P < 0.005) serum levels of ALS (Fig. 1Go, lower panel) regardless of the administration pattern (P = 0.26) from 94 ± 21 to 180 ± 29 nmol/L (infusion) and from 85 ± 17 to 155 ± 17 nmol/L (pulses).



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  		Figure 1. Serum concentrations of IGF-I (micrograms per L; upper panel), IGFBP-3 (micrograms per L; middle panel), and ALS (nanomoles per L; lower panel) before ({blacksquare}) and after ({square}) iv administration of GH as a continuous infusion (left) or eight identical doses injected every 3.5 h (right). *, P < 0.01 (without GH vs. with GH).

 
The IGF-I/IGFBP-3 molar ratio (Fig. 2Go, upper panel) increased significantly (both P < 0.01) during the initial 36 h of GH exposure. The changes occurred regardless of the GH pattern (P = 0.23). Similarly, the ALS/IGFBP-3 molar ratio (Fig. 2Go, lower panel) increased in response to GH, but was unaffected by the GH pattern (P = 0.72).



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  		Figure 2. IGF-I/IGFBP-3 molar ratio (upper panel), and ALS/IGFBP-3 molar ratio (lower panel) before ({blacksquare}) and after ({square}) iv administration of GH as a continuous infusion (left) or eight identical doses injected every 3.5 h (right). *, P < 0.01 (without GH vs. with GH).

 
The increase in all three single components of the ternary complex after acute GH administration was accompanied by increased formation of the ternary complex-associated IGFBP-3 (Fig. 3Go, upper panel). Bound IGFBP-3 levels rose by 44% during GH infusion (from 1062 ± 231 to 1524 ± 328 µg/L; P = 0.048) and by 62% after pulses (from 970 ± 318 to 1574 ± 272 µg/L; P = 0.004). The noncomplex-associated IGFBP-3 levels (Fig. 3Go, lower panel), on the other hand, were not increased by GH [infusion, from 290 ± 51 to 266 ± 23 µg/L (P = 0.49); pulses, from 355 ± 70 to 294 ± 37 µg/L (P = 0.50)]. The different patterns of GH delivery did not influence ternary complex formation (P = 0.77).



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  		Figure 3. Serum concentrations (micrograms per L) of the 150-kDa ternary complex-associated IGFBP-3 fraction (upper panel) and the noncomplex-associated fraction (lower panel) before ({blacksquare}) and after ({square}) iv administration of GH as a continuous infusion (left) or eight identical doses injected every 3.5 h (right). *, P < 0.05 (without GH vs. with GH).

 
In Fig. 4Go representative examples of the IGFBP-3 fractions, as assessed by size exclusion chromatography, before and after bolus injections (upper panel) or continuous infusion (lower panel) of GH are depicted.



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  		Figure 4. Characterization of the IGFBP regions after size exclusion chromatography in a representative GHD patient before (upper panel) and after (lower panel) iv GH administration as continuous infusion (top panel) and pulses (bottom panel), respectively. After chromatography, 50 µL from each fraction were subjected to Western ligand blotting (WLB). IGFBP-3 appears in the WLB as a 38-/42-kDa doublet in the 150-kDa ternary complex and the 45-kDa (non-150-kDa) ternary complex form. Note the rise in IGFBP-3 in the 150-kDa ternary complex in the IGFBP regions in response to GH administration.

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
During GH therapy in GHD patients IGF-I is a widely used marker of the efficacy of treatment. However, the half-life of IGF-I and the bioactivity of IGF-I are dependent on the degree to which IGF-I is incorporated in the ternary complex with IGFBP-3 and ALS. In animal models GH administration to GHD rats is followed by increases in IGF-I, IGFBP-3, and formation of the ternary complex (8). However, studies in humans, showing increased levels of the single components of the ternary complex, have not reported data on ternary complex formation.

The major new findings of the present study were that GH administration in GHD patients induced formation of the ternary complex during short-term GH administration, while the noncomplex-bound levels of IGFBP-3 were unchanged. Further, the mode of GH administration (i.e. continuous or pulsatile) seems to be equally efficient in stimulating formation of the ternary complex.

Previous studies in man on the impact of the mode of GH administration have somewhat counterintuitively shown that continuous GH delivery is at least as effective as intermittent administration with respect to increasing serum IGF-I and other biochemical indexes of GH action (13, 17). In GHD rats the 150-kDa ternary complex is induced more effectively by continuous than by pulsatile GH administration (8). This could theoretically explain why continuous GH infusion is superior to pulsatile delivery in reducing body fat in a study in obese rats (18), although most studies in rats have reported that a pulsatile GH pattern generates serum and tissue IGF-I levels more effectively (9). Other parameters that have been shown to be differently regulated by pulsatile and constant GH patterns in rodents, such as GHBP (19, 20), and certain lipoproteins (21, 22), however, have been shown to depend less on the GH pattern in humans (12, 23).

A recent study in GHD children (6) reported that an increased growth rate in response to GH therapy was strongly related to changes in ternary complex-associated IGF-I and IGFBP-3. Thus, when monitoring the effects of GH therapy, serum levels of IGF-I and IGFBP-3 may in the future be supplemented with assessment of ternary complex formation at least in some patients. As opposed to animal data (8), data from the present study indicate that continuous and pulsatile GH administration patterns affect ternary complex formation similarly in GHD humans. The significance of this finding in relation to the rather small differences in the circulating levels of IGF-I and IGFBP-3 reported in previous studies (13, 17) is unknown.

The molar ratio between IGF-I and IGFBP-3 has been proposed as an index of bioavailable IGF-I (24). The increase in the ratio after GH administration indicates that the bioavailable IGF-I fraction is increased shortly after GH administration is initiated, but the clinical significance of this is unknown. It should be recognized, however, that the majority of the binding sites on IGFBP-3 are occupied by IGF-II. As ALS may help to stabilize the ternary complex, the molar ratio between ALS and IGFBP-3 has been suggested to serve as an reflection of the quantitative formation of the complex, and thus of the amount of bound IGF-I (25). According to the present data, the ratio was increased by GH administration.

In summary, continuous GH exposure was superior to a pulsatile pattern in increasing serum IGF-I levels. GH administration to GHD patients increased circulating levels of IGF-I, IGFBP-3, and ALS and the IGF-I/IGFBP-3 molar ratio. In parallel to this, GH administration induced an increased formation of the 150-kDa ternary complex itself. The noncomplex-associated IGFBP-3 fraction was unaffected by GH treatment. The GH administration pattern did not seem to influence the magnitude of ternary complex formation. Longer term studies in GH-deficient patients comparing GH patterns during steady state treatment have reported higher serum levels of IGF-I and IGFBP-3 during continuous GH delivery (26). Accordingly, in future studies it may be interesting to measure 150-kDa ternary complex formation after longer term continuous and pulsatile GH administration patterns.


   Acknowledgments
 
GH was generously supplied by Novo Nordisk A/S (Gentofte, Denmark).


   Footnotes
 
1 This work was supported by the Danish Medical Research Council (Grant 9700592), the Novo Foundation, the Nordic Insulin Foundation, the Johanne and Aage Louis Petersen Foundation, the Eva and Henry Frænkel Memorial Foundation, and the Aarhus University-Novo Nordisk Center for Research in Growth and Regeneration (Danish Medical Research Council Grant 9600822). Back

Received December 30, 1999.

Revised March 17, 2000.

Revised May 8, 2000.

Accepted July 20, 2000.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Baxter RC. 1988 Characterization of the acid-labile subunit of the growth hormone-dependent insulin-like growth factor binding protein complex. J Clin Endocrinol Metab. 67:265–272.[Abstract]
  2. Lewitt MS, Saunders H, Phuyal JL, Baxter RC. 1994 Complex formation by human insulin-like growth factor-binding protein 3 and human acid-labile subunit in growth hormone-deficient rats. Endocrinology. 134:2404–2409.[Abstract]
  3. Baxter RC, Martin JL, Beniac VA. 1989 High molecular weight insulin-like growth factor binding protein complex. Purification and properties of the acid-labile subunit from human serum. J Biol Chem. 264:11843–11848.[Abstract/Free Full Text]
  4. Baxter RC. 1994 Insulin-like growth factor binding proteins in the human circulation: a review. Horm Res. 42:140–144.[Medline]
  5. Barreca A, Ponzani P, Arvigo M, Giordano G, Minuto F. 1995 Effect of the acid-labile subunit on the binding of insulin-like growth factor (IGF)-binding protein 3 to 125I- IGF-I. J Clin Endocrinol Metab. 80:1318–1324.[Abstract]
  6. Mandel SH, Moreland E, Rosenfeld RG, Gargosky SE. 1997 The effect of GH therapy on the immunoreactive forms and distribution of IGFBP-3, IGF-I, the acid-labile subunit, and growth rate in GH-deficient children. Endocrine. 7:351–360.[Medline]
  7. Baxter RC, Skriver L. 1993 Altered ligand specificity of proteolysed insulin-like growth factor binding protein-3. Biochem Biophys Res Commun. 196:1267–1273.[CrossRef][Medline]
  8. Gargosky SE, Tapanainen P, Rosenfeld RG. 1994 Administration of growth hormone (GH), but not insulin-like growth factor I (IGF-I), by continuous infusion can induce the formation of the 150-kilodalton IGF-binding protein 3 complex in GH-deficient rats. Endocrinology. 134:2267–2276.[Abstract]
  9. Isgaard J, Carlsson L, Isaksson OG, Jansson JO. 1988 Pulsatile intravenous growth hormone (GH) infusion to hypophysectomized rats increases insulin-like growth factor I messenger ribonucleic acid in skeletal tissues more effectively than continuous GH infusion. Endocrinology. 123:2605–2610.[Abstract]
  10. Jørgensen JO, Møller N, Lauritzen T, Christiansen JS. 1990 Pulsatile versus continuous intravenous administration of growth hormone (GH) in GH-deficient patients: effects on circulating insulin-like growth factor I and metabolic indices. J Clin Endocrinol Metab. 70:1616–1623.[Abstract]
  11. Maiter D, Underwood LE, Maes M, Davenport ML, Ketelslegers JM. 1988 Different effects of intermittent and continuous growth hormone (GH) administration on serum somatomedin-C/insulin-like growth factor I and liver GH receptors in hypophysectomized rats. Endocrinology. 123:1053–1059.[Abstract]
  12. Laursen T, Jørgensen JOL, Ho KKY, Møller J, Christiansen JS. 1997 Serum concentrations of growth hormone (GH) binding protein in GH-deficient patients: impact of mode of GH administration. Endocrinol Metab. 4:281–287.
  13. Laursen T, Jørgensen JOL, Christiansen JS. 1994 Metabolic response to growth hormone (GH) administered in a pulsatile, continuous or combined pattern. Endocrinol Metab. 1:33–40.
  14. Frystyk J, Dinesen B, Ørskov H. 1995 Non-competitive time-resolved immunofluorometric assays for determination of human insulin-like growth factor I and II. Growth Regul. 5:169–176.[Medline]
  15. Baxter RC. 1990 Circulating levels and molecular distribution of the acid-labile ({alpha}) subunit of the high molecular weight insulin-like growth factor-binding protein complex. J Clin Endocrinol Metab. 70:1347–1353.[Abstract]
  16. Hossenlopp P, Segovia B, Lassarre C, Roghani M, Bredon M, Binoux M. 1990 Evidence of enzymatic degradation of insulin-like growth factor-binding proteins in the 150 kDa complex during pregnancy. J Clin Endocrinol Metab. 71:797–805.[Abstract]
  17. Laursen T, Jørgensen JOL, Jakobsen G, Hansen BL, Christiansen JS. 1995 Continuous infusion versus daily injections of growth hormone (GH) for 4 weeks in GH-deficient patients. J Clin Endocrinol Metab. 80:2410–2418.[Abstract]
  18. Clark RG, Mortensen DL, Carlsson LM, Carlsson B, Carmignac D, Robinson IC. 1996 The obese growth hormone (GH)-deficient dwarf rat: body fat responses to patterned delivery of GH and insulin-like growth factor I. Endocrinology. 137:1904–1912.[Abstract]
  19. Maiter D, Walker JL, Adam E, et al. 1992 Differential regulation by growth hormone (GH) of insulin-like growth factor I and GH receptor/binding protein gene expression in rat liver. Endocrinology. 130:3257–3264.
  20. Bick T, Hochberg Z, Amit T, Isaksson OG, Jansson JO. 1992 Roles of pulsatility and continuity of growth hormone (GH) administration in the regulation of hepatic GH-receptors, and circulating GH-binding protein and insulin-like growth factor I. Endocrinology. 131:423–429.[Abstract]
  21. Oscarsson J, Olofsson SO, Bondjers G, Eden S. 1989 Differential effects of continuous versus intermittent administration of growth hormone to hypophysectomized female rats on serum lipoproteins and their apoproteins. Endocrinology. 125:1638–1649.[Abstract]
  22. Sjöberg A, Oscarsson J, Edén S, Olofsson S-O. 1994 Continuous but not intermittent administration of growth hormone to hypophysectomized rats increases apolipoprotein-E secretion from cultured hepatocytes. Endocrinology. 134:790–798.[Abstract]
  23. Laursen T, Lemming L, Jørgensen JO, Klausen IC, Christiansen JS. 1998 Different effects of continuous and intermittent patterns of growth hormone administration on lipoprotein levels in growth hormone-deficient patients. Horm Res. 50:284–291.[CrossRef][Medline]
  24. Juul A, Main K, Blum WF, Lindholm J, Ranke MB, Skakkebaek NE. 1994 The ratio between serum levels of insulin-like growth factor (IGF)-I and the IGF binding proteins (IGFBP-1, 2 and 3) decreases with age in healthy adults and is increased in acromegalic patients. Clin Endocrinol (Oxf). 41:85–93.[Medline]
  25. Baxter RC. 1997 The binding protein’s binding protein-clinical applications of acid-labile subunit (ALS) measurement. J Clin Endocrinol Metab. 82:3941–3943.[Free Full Text]
  26. Johansson JO, Oscarsson J, Bjarnason R, Bengtsson BA. 1996 Two weeks of daily injections and continuous infusion of recombinant human growth hormone (GH) in GH-deficient adults. I. Effects on insulin-like growth factor I (IGF-I), GH and IGF binding proteins, and glucose homeostasis. Metabolism. 45:362–369.[CrossRef][Medline]



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