Growth hormone-binding protein-related immunoreactivity in the serum of patients with acromegaly is regulated inversely by growth hormone concentration

1995 ◽  
Vol 132 (3) ◽  
pp. 306-312 ◽  
Author(s):  
Jürgen Kratzsch ◽  
Werner F Blum ◽  
Manfred Ventz ◽  
Thomas Selisko ◽  
Gerd Birkenmeyer ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Binding Protein ◽  
Receptor Density ◽  
Hormone Concentration ◽  
Hormone Binding ◽  
Gh Receptor ◽  
Growth Hormone Binding Protein ◽  
Igf I ◽  
Hormone Binding Protein ◽  
Igfbp 3

Kratzsch J. Blum WF, Ventz M, Selisko T, Birkenmeyer G, Keller E. Growth hormone-binding proteinrelated immunoreactivity in the serum of patients with acromegaly is regulated inversely by growth hormone concentration. Eur J Endocrinol 1994;132:306–12. ISSN 0804–4643 In this report we describe a newly developed radioimmunoassay (RIA) for the determination of the high-affinity growth hormone-binding protein (GHBP) in human blood. Using this RIA for the measurement of GHBP in serum of 29 patients with acromegaly, decreased concentrations were found compared to the normal range, depending on the activity of the disease. Growth hormonebinding protein was correlated inversely to log GH (r = −0.7, p < 0.001). A weaker relationship was shown between the GHBP activity determined in a functional assay based on charcoal separation and log GH (r = −0.51, p< 0.01). While insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3) were correlated directly to log GH (r = 0.77 and r = 0.66, p < 0.001), an inverse and weaker relationship was evident between GHBP measured by RIA and IGF-I or IGFBP-3 (r = −0.61 and r = −0.57,p < 0.01). In contrast, no correlation could be detected between data of the functional GHBP assay and IGF-I or IGFBP-3, These results suggest, that: (1) in patients with acromegaly the GH receptor density in tissue reflected by the GHBP serum levels seems to be down-regulated, depending on the increased GH level; (2) low GHBP concentrations indicate an active disease in acromegaly and may be of diagnostic interest; (3) presuming that the GH receptor density is related to GH sensitivity, the variation of GH sensitivity is less important for IGF-I and IGFBP-3 production than the circulating GH concentration, at least in the situation of acromegaly; (4) because endogenous GH does not interfere in that assay, the RIA provides a valuable tool for the investigation of regulations between GH, GHBP and the GH receptor, especially in patients with acromegaly. The GHBP levels may be used as a sensitive parameter of GH oversecretion and tissue sensitivity to this hormone. Jürgen Kratzsch, Inst. Clin. Chem., University of Leipzig, Paul-List-Str. 13–15, D-04103 Leipzig, Germany

Comparison between the human serum growth hormone-binding protein and the water-soluble growth hormone-binding site released from IM-9 lymphocytes

1993 ◽  
Vol 129 (6) ◽  
pp. 559-564 ◽  
Author(s):  
Guy Massa ◽  
Mapoko Ilondo ◽  
Magda Vanderschueren-Lodeweyckx
Keyword(s):  
Growth Hormone ◽  
Human Serum ◽  
Binding Site ◽  
Binding Protein ◽  
Water Soluble ◽  
Hormone Binding ◽  
Serum Growth Hormone ◽  
Gh Receptor ◽  
Growth Hormone Binding Protein ◽  
Hormone Binding Protein

The characteristics of the human serum growth hormone-binding protein (GHBP) were compared with those of a water-soluble GH-binding site prepared by incubating cultured IM-9 lymphocytes in assay buffer with 25 mmol/l iodoacetamide. High-performance liquid chromatography gel filtration of the water-soluble GH-binding site incubated with 125I-labeled human GH ([125I]hGH) revealed a large peak of bound [125I]hGH eluting at the same position as the peak of [125I]hGH bound to the GHBP in serum. The estimated Mr of the peak was 120 000, presumably representing one [125I]hGH bound to two binding sites. The binding specificities of the serum GHBP, the water-soluble GH-binding site and the GH receptor on IM-9 lymphocytes were identical. The binding affinities for 22 000 hGH and for 20 000 hGH of the serum GHBP were similar to the binding affinity of the water-soluble GH-binding site but lower than those of the cellular GH receptor. These findings show that the characteristics of the serum GHBP are comparable to those of the water-soluble GH-binding site released from IM-9 cells and support the hypothesis that in man the serum GHBP is produced by proteolytic cleavage of the cellular GH receptor.

Growth hormone binding protein and growth hormone availability in acromegalic patients treated with long-acting octreotide (Sandostatin-LAR)

1997 ◽  
Vol 136 (1) ◽  
pp. 61-66 ◽  
Author(s):  
Sanne Fisker ◽  
Andreas Kaal ◽  
Marcella Montini ◽  
Alberto Pedroncelli ◽  
Giorgio Pagani ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Binding Protein ◽  
Hormone Binding ◽  
Age And Gender ◽  
Growth Hormone Binding Protein ◽  
Igf I ◽  
Octreotide Treatment ◽  
Hormone Binding Protein ◽  
And Gender ◽  
Long Acting

Abstract Objective: In the medical treatment of acromegaly different factors are influencial; among these the impact on growth hormone binding protein (GHBP) has not been clarified. Design: Twenty acromegalic patients and nineteen age- and gender-matched normal subjects participated in this study. The patients were treated for 21 months with depot long-acting microsphere-enclosed octreotide (Sandostatin-LAR). Previously, all the patients were treated s.c. with octreotide t.i.d. After a 2-week wash-out period (baseline) the patients received the first i.m. injection of the long-acting octreotide. The first two injections were administered at 60-day intervals; thereafter the injections were at 28-day intervals. Methods: The levels of GHBP, complexed GHBP, growth hormone (GH) and insulin-like growth factor-I (IGF-I) were determined in fasting serum samples. Results: In the 2-week wash-out period GHBP levels decreased from 1·13 ± 0·17 to 0·92 ± 0·15 nmol/l (P < 0·05). During the 21-months treatment, GHBP increased again to 1·10 ± 0·16 nmol/l. In the age- and gender-matched control group GHBP levels were significantly higher at all times (1·95 ± 0·21 nmol/l, P(all) < 0·02). Mean levels of 8-h GH decreased from 12·6 ± 2·58 μg/l at baseline to 1·97 ± 0·20 μg/l after 21 months of treatment (P < 0·05). Mean 8-h GH levels were unchanged during long-acting octreotide treatment compared with levels during s.c. treatment (1·97 ± 0·20 μg/l and 1·90 ± 0·20 μg/l respectively). In fasting blood samples GH-complexed GHBP ranged from 13·8 ± 2·4% (9 months) to 25·4 ± 4·5% (baseline) of total GHBP. Serum IGF-I increased from 367 ± 45 to 764 ± 80 μg/l (P < 0·05) during the 2-week wash-out period and decreased to 290 ± 35 μg/l (P < 0·05) after 21 months of treatment with long-acting octreotide. IGF-I levels after 21 months were significantly lower than during s.c. octreotide treatment (P < 0·05). Conclusion: Serum GHBP levels are similar during treatment with long-acting octreotide as compared with regular octreotide. Furthermore, significant changes in GHBP can occur within 2 weeks. Finally, in addition to the lowering effect on GH levels, the induced increase in GHBP levels may imply a further advantage in octreotide treatment of acromegaly, circulating GH bound to GHBP may less readily reach the tissues. European Journal of Endocrinology 136 61–66

scholarly journals Plasma growth hormone and growth hormone-binding protein during development in the marsupial brushtail possum (Trichosurus vulpecula)

2002 ◽  
Vol 173 (3) ◽  
pp. 507-515 ◽  
Author(s):  
MC Saunders ◽  
RT Gemmell ◽  
MJ Waters ◽  
JD Curlewis
Keyword(s):  
Growth Hormone ◽  
Binding Protein ◽  
Post Partum ◽  
Brushtail Possum ◽  
Trichosurus Vulpecula ◽  
Hormone Binding ◽  
Adult Individual ◽  
Gh Receptor ◽  
Growth Hormone Binding Protein ◽  
Hormone Binding Protein

Plasma concentrations of growth hormone (GH) were measured in the brushtail possum (Trichosurus vulpecula) pouch young from 25 through to 198 days post-partum (n=71). GH concentrations were highest early in pouch life (around 100 ng/ml), and thereafter declined in an exponential fashion to reach adult concentrations (10.8+/-1.8 ng/ml; n=21) by approximately 121-145 days post-partum, one to two months before the young is weaned. Growth hormone-binding protein (GHBP), which has been shown to modify the cellular actions of GH in eutherian mammals, was identified for the first time in a marsupial. Based on size exclusion gel filtration, possum GHBP had an estimated molecular mass of approximately 65 kDa, similar to that identified in other mammalian species, and binding of (125)I-labelled human GH (hGH) was displaced by excess hGH (20 microg). An immunoprecipitation method, in which plasma GHBP was rendered polyethylene glycol precipitable with a monoclonal antibody to the rabbit GHBP/GH receptor (MAb 43) and labelled with (125)I-hGH, was used to quantitate plasma GHBP by Scatchard analysis in the developing (pooled plasma samples) and adult (individual animals) possums. Binding affinity (K(a)) values in pouch young aged between 45 and 54 and 144 and 153 days post-partum varied between 1.0 and 2.4 x 10(9)/M, which was slightly higher than that in adult plasma (0.96+/-0.2 x 10(9)/M, n=6). Binding capacity (B(max)) values increased from non-detectable levels in animals aged 25-38 days post-partum to reach concentrations around half that seen in the adult (1.4+/-0.2 x 10(-9) M) by about 117 days post-partum and remained at this level until 153 days post-partum. Therefore, in early pouch life when plasma GH concentrations are highest, the very low concentrations of GHBP are unlikely to be important in terms of competing with GH-receptor for ligand or altering the half-life of circulating GH.

Differential effects of octreotide treatment and transsphenoidal surgery on growth hormone—binding protein levels in patients with acromegaly

1999 ◽  
Vol 90 (4) ◽  
pp. 647-650 ◽  
Author(s):  
Irma Hernandez ◽  
Daniela Soderlund ◽  
Ana Laura Espinosa-de-los-Monteros ◽  
Raquel Ochoa ◽  
Arturo Zarate ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Transsphenoidal Surgery ◽  
Binding Protein ◽  
Hormone Binding ◽  
Content Type ◽  
Growth Hormone Binding Protein ◽  
Igf I ◽  
Octreotide Treatment ◽  
Hormone Binding Protein ◽  
Fine Print

Object. The high-affinity growth hormone—binding protein (GHBP) represents the extracellular portion of the growth hormone (GH) receptor, and its serum levels are a reflection of the tissue receptor status. Levels of GHBP are decreased in patients with active acromegaly, probably because of downregulation of GH receptors. However, there are no studies of patients with acromegaly in which the effects of medical (that is, administration of somatostatin analogs) and surgical therapy on GHBP levels have been compared. That is the task the authors set out to accomplish in this study.Methods. The authors studied seven patients in whom acromegaly had been recently diagnosed. They examined these patients at baseline, 2 months after octreotide treatment (subcutaneous administration of 100 µg octreotide three times per day), and 1 month after transsphenoidal surgery. Growth hormone—binding activity was measured, as well as the following biochemical markers of the somatotropic axis: GH suppression induced by oral administration of glucose, insulin-like growth factor-I (IGF-I), and insulin-like growth factor—binding protein-3 (IGFBP3). Although octreotide treatment induced a decrease in the levels of GH, IGF-I, and IGFBP3, as well as an increase in the level of GHBP, these biochemical markers did not reach normal levels. On the other hand, after transsphenoidal surgery, GHBP levels became normal, particularly in those patients in whom serum GH could be suppressed to an undetectable level after glucose loading.Conclusions. The authors conclude that persistently low GHBP levels in patients with acromegaly are normalized by successful pituitary surgery and correlate well with disease activity.

In rats with sepsis, the acute fall in IGF-I is associated with an increase in circulating growth hormone-binding protein levels

2000 ◽  
Vol 26 (10) ◽  
pp. 1547-1552 ◽  
Author(s):  
M.J. O'Leary ◽  
N. Quinton ◽  
C.N. Ferguson ◽  
V.R. Preedy ◽  
R.J.M. Ross ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Binding Protein ◽  
Hormone Binding ◽  
Protein Levels ◽  
Growth Hormone Binding Protein ◽  
Igf I ◽  
Hormone Binding Protein

scholarly journals Progressive Normalization of Growth Hormone-Binding Protein and IGF-I Levels in Treated Growth Hormone-Deficient Children

1995 ◽  
Vol 37 (6) ◽  
pp. 731-735 ◽  
Author(s):  
Juliane Leger ◽  
Michèle Noel ◽  
Paul Czernichow ◽  
Marie-Catherine Postel-Vinay
Keyword(s):  
Growth Hormone ◽  
Binding Protein ◽  
Hormone Binding ◽  
Growth Hormone Binding Protein ◽  
Igf I ◽  
Hormone Binding Protein

High-affinity growth hormone binding protein, insulin-like growth factor I and insulin-like growth factor binding protein 3 in adults with growth hormone deficiency

1996 ◽  
Vol 135 (1) ◽  
pp. 82-86 ◽  
Author(s):  
Corné A Roelen ◽  
Hans P Koppeschaar ◽  
Wouter R de Vries ◽  
Pierre M Zelissen ◽  
Yvonne E Snel ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Gh Deficiency ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
High Affinity ◽  
Growth Hormone Binding Protein ◽  
Igf I ◽  
Hormone Binding Protein ◽  
Igfbp 3

Roelen CA, Koppeschaar HP, de Vries WR, Zelissen PM, Snel YE, Doerga ME, Thijssen JH, Blankenstein RA. High-affinity growth hormone binding protein, insulin-like growth factor I and insulin-like growth factor binding protein 3 in adults with growth hormone deficiency. Eur J Endocrinol 1996;135:82–6. ISSN 0804–4643 The high-affinity growth hormone binding protein (GHBP) circulates in human blood and represents the extracellular domain of the growth hormone (GH) receptor. The effects of GH deficiency on GHBP in adults are not clear. The aim of this study was to evaluate serum GHBP levels in adults with GH deficiency and to assess whether GHBP measurement may contribute to the diagnosis of adult GH deficiency, based on a two-step model. We measured insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP-3) and GHBP levels in serum samples of 36 patients with adult-onset GH deficiency. The GHBP levels were measured by FPLC size-exclusion chromatography; IGF-I and IGFBP-3 levels were measured by RIA. Serum GHBP levels were elevated above the upper limit of the 95% confidence interval in 26 patients, whereas IGF-I and IGFBP-3 levels were low in 10 patients and in 16 patients, respectively. The combination of low serum IGF-I and low IGFBP-3 levels was found in 10 patients. In nine patients, serum IGF-I levels were low, with elevated GHBP levels. Low serum IGF-I, low IGFBP-3 and elevated GHBP levels were found in five patients. Only four out of 36 patients had serum IGF-I, IGFBP-3 and GHBP levels that were within the 95% confidence interval of the control values. We conclude that adults with acquired GH deficiency have elevated GHBP levels in comparison to healthy subjects. We suggest that measurement of GHBP levels might contribute to the diagnosis of adult GH deficiency, though further research is required to study the additional value of GHBP measurements. HPF Koppeschaar, Department of Endocrinology, University Hospital Utrecht, HPL00.407, PO Box 85500, 3508 GA Utrecht, The Netherlands

scholarly journals Effect of intraperitoneal insulin delivery on growth hormone binding protein, insulin-like growth factor (IGF)-I, and IGF-binding protein-3 in IDDM

Diabetologia ◽  
1996 ◽  
Vol 39 (12) ◽  
pp. 1498-1504 ◽  
Author(s):  
H. Hanaire-Broutin ◽  
B. Sallerin-Caute ◽  
M. F. Poncet ◽  
M. Tauber ◽  
R. Bastide ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Binding Protein ◽  
Hormone Binding ◽  
Growth Hormone Binding Protein ◽  
Igf I ◽  
Igf Binding ◽  
Hormone Binding Protein ◽  
Intraperitoneal Insulin ◽  
Igf Binding Protein
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