High levels of 150-kDa insulin-like growth factor binding protein three ternary complex in patients with acromegaly and the effect of pegvisomant-induced serum IGF-I normalization.

2.50
Hdl Handle:
http://hdl.handle.net/10541/77931
Title:
High levels of 150-kDa insulin-like growth factor binding protein three ternary complex in patients with acromegaly and the effect of pegvisomant-induced serum IGF-I normalization.
Authors:
Parkinson, Craig; Flyvbjerg, Allan; Trainer, Peter J
Abstract:
OBJECTIVE: To assess the effect of pegvisomant-induced serum insulin-like growth factor 1 (IGF-1) normalization on IGF binding proteins 1, 2, 3 (IGFBP-1, IGFBP-2 and IGFBP-3), total, non-bound (45 kDa) and 150-kDa ternary complex-associated IGFBP-3, and in vivo IGFBP-3 proteolysis in patients with active acromegaly. DESIGN: The above parameters were measured in 16 patients (median age 57 (range 27-78)) with active acromegaly (serum IGF-I at least 30% above the upper limit of an age-related reference range after washout) in a paired manner on samples obtained after washout and the first occurrence of serum IGF-I normalization during pegvisomant therapy (median dose 15 mg/day (10-40 mg)). RESULTS: Total IGFBP-3 and 150-kDa ternary complex-associated IGFBP-3 were significantly elevated in patients at baseline compared to controls ((mean+/-SEM) 4345+/-194 vs. 3456+/-159 microg/L, P<0.01 and 3908+/-160 va. 3042+/-149 microg/L, P<0.01, respectively), but no significant difference in 45-kDa IGFBP-3 or in vivo IGFBP-3 proteolysis was observed. Serum IGF-I normalization (699+/-76 to 242+/-28 microg/L, P<0.0001) was associated with a fall in total IGFBP-3 (4345+/-194 to 3283+/-160 microg/L, P<0.001) due to a reduction in 150-kDa ternary complex-associated IGFBP-3 (3908+/-160 to 3008+/-140 microg/L, P<0.0001). 45 kDa IGFBP-3 and in vivo IGFBP-3 proteolysis were unaffected by GH receptor blockade (326+/-13 to 330+/-18 microg/L, P=0.86; 30+/-3.5 to 30+/-3.9%, P=0.75, respectively). CONCLUSIONS: GH receptor blockade in patients with acromegaly lowers IGF-I and 150-kDa IGFBP-3 ternary complex formation. 50 kDa ternary complex formation (not in vivo IGFBP-3 proteolysis) is GH dependent and measurement of 150-kDa ternary complex-associated IGFBP-3 may provide useful information regarding treatment efficacy in patients with acromegaly.
Affiliation:
Department of Diabetes and Endocrinology, The Ipswich Hospital, Heath Road, Ipswich, Suffolk IP4 5PD, UK. craig.parkinson@isph-tr.anglox.nhs.uk
Citation:
High levels of 150-kDa insulin-like growth factor binding protein three ternary complex in patients with acromegaly and the effect of pegvisomant-induced serum IGF-I normalization. 2004, 14 (1):59-65 Growth Horm. IGF Res.
Journal:
Growth Hormone & IGF Research
Issue Date:
Feb-2004
URI:
http://hdl.handle.net/10541/77931
DOI:
10.1016/j.ghir.2003.08.004
PubMed ID:
14700556
Type:
Article
Language:
en
ISSN:
1096-6374
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorParkinson, Craig-
dc.contributor.authorFlyvbjerg, Allan-
dc.contributor.authorTrainer, Peter J-
dc.date.accessioned2009-08-19T16:22:56Z-
dc.date.available2009-08-19T16:22:56Z-
dc.date.issued2004-02-
dc.identifier.citationHigh levels of 150-kDa insulin-like growth factor binding protein three ternary complex in patients with acromegaly and the effect of pegvisomant-induced serum IGF-I normalization. 2004, 14 (1):59-65 Growth Horm. IGF Res.en
dc.identifier.issn1096-6374-
dc.identifier.pmid14700556-
dc.identifier.doi10.1016/j.ghir.2003.08.004-
dc.identifier.urihttp://hdl.handle.net/10541/77931-
dc.description.abstractOBJECTIVE: To assess the effect of pegvisomant-induced serum insulin-like growth factor 1 (IGF-1) normalization on IGF binding proteins 1, 2, 3 (IGFBP-1, IGFBP-2 and IGFBP-3), total, non-bound (45 kDa) and 150-kDa ternary complex-associated IGFBP-3, and in vivo IGFBP-3 proteolysis in patients with active acromegaly. DESIGN: The above parameters were measured in 16 patients (median age 57 (range 27-78)) with active acromegaly (serum IGF-I at least 30% above the upper limit of an age-related reference range after washout) in a paired manner on samples obtained after washout and the first occurrence of serum IGF-I normalization during pegvisomant therapy (median dose 15 mg/day (10-40 mg)). RESULTS: Total IGFBP-3 and 150-kDa ternary complex-associated IGFBP-3 were significantly elevated in patients at baseline compared to controls ((mean+/-SEM) 4345+/-194 vs. 3456+/-159 microg/L, P<0.01 and 3908+/-160 va. 3042+/-149 microg/L, P<0.01, respectively), but no significant difference in 45-kDa IGFBP-3 or in vivo IGFBP-3 proteolysis was observed. Serum IGF-I normalization (699+/-76 to 242+/-28 microg/L, P<0.0001) was associated with a fall in total IGFBP-3 (4345+/-194 to 3283+/-160 microg/L, P<0.001) due to a reduction in 150-kDa ternary complex-associated IGFBP-3 (3908+/-160 to 3008+/-140 microg/L, P<0.0001). 45 kDa IGFBP-3 and in vivo IGFBP-3 proteolysis were unaffected by GH receptor blockade (326+/-13 to 330+/-18 microg/L, P=0.86; 30+/-3.5 to 30+/-3.9%, P=0.75, respectively). CONCLUSIONS: GH receptor blockade in patients with acromegaly lowers IGF-I and 150-kDa IGFBP-3 ternary complex formation. 50 kDa ternary complex formation (not in vivo IGFBP-3 proteolysis) is GH dependent and measurement of 150-kDa ternary complex-associated IGFBP-3 may provide useful information regarding treatment efficacy in patients with acromegaly.en
dc.language.isoenen
dc.subject.meshAcromegaly-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshDouble-Blind Method-
dc.subject.meshFemale-
dc.subject.meshHuman Growth Hormone-
dc.subject.meshHumans-
dc.subject.meshInsulin-Like Growth Factor Binding Protein 1-
dc.subject.meshInsulin-Like Growth Factor Binding Protein 2-
dc.subject.meshInsulin-Like Growth Factor Binding Protein 3-
dc.subject.meshInsulin-Like Growth Factor I-
dc.subject.meshInsulin-Like Growth Factor II-
dc.subject.meshMacromolecular Substances-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshReference Values-
dc.titleHigh levels of 150-kDa insulin-like growth factor binding protein three ternary complex in patients with acromegaly and the effect of pegvisomant-induced serum IGF-I normalization.en
dc.typeArticleen
dc.contributor.departmentDepartment of Diabetes and Endocrinology, The Ipswich Hospital, Heath Road, Ipswich, Suffolk IP4 5PD, UK. craig.parkinson@isph-tr.anglox.nhs.uken
dc.identifier.journalGrowth Hormone & IGF Researchen

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.