Size heterogeneity of circulating growth hormone in acromegaly. 'Big-city' GH forms are associated with inappropriately low IGF-I levels

M. Arosio, M. Nissim, M. Ballabio, R. Orefice, N. Bazzoni, G. Faglia

Research output: Contribution to journalArticle

Abstract

Circulating GH consists of several molecular size species with different biological activity. A reduced sensitivity of some monoclonal antibodies towards high molecular weight GH variants has been reported. The aim of the present work was to evaluate the molecular size species of circulating GH using Sephadex G-100 gel filtration chromatography in acromegalic patients and in normal subjects employing both RIA and an immunoradiometric assay for all GH determinations. In 6 normal subjects, studied under GHRH stimulation, little GH was 69.8 ± 6% (mean ±SD), big GH (44 kD) 26.4 ± 6% and big-big GH (>80 kD) 2.8 ± 4%, in IRMA, with a good correspondence with RIA results (70.8 ± 8, 27.0 ± 4, and 3.2 ± 2%, respectively). In 13 untreated acromegalic patients, studied in basal conditions, the little form constituted 76.2 ± 7%, the big form 18.3 ± 4%, which is significantly lower than in normals (p90 kD), not recognized by IRMA. All IRMA immunoreactivity eluted with a K(av) corresponding to 19-50 kD. In conclusion: a. the three main molecular size isomers of serum GH are similarly recognized by IRMA and RIA methods in normal subjects. b. in acromegaly, both quantitative and qualitative modifications of the GH chromatographic profile may be present. In particular, increased amounts of big-big forms, whether or not recognized by monoclonal antibodies, have been observed. Their lower bioactivity, suggested by the normal or lower than expected IGF-I levels, can account for the discrepancy between serum GH levels and the clinical picture or IGF-I levels sometimes observed in acromegaly.

Original languageEnglish
Pages (from-to)150-159
Number of pages10
JournalActa Endocrinologica
Volume125
Issue number2
Publication statusPublished - 1991

Fingerprint

Acromegaly
Insulin-Like Growth Factor I
Growth Hormone
Monoclonal Antibodies
Immunoradiometric Assay
Serum
Gel Chromatography
Molecular Weight
sephadex

ASJC Scopus subject areas

  • Endocrinology

Cite this

Size heterogeneity of circulating growth hormone in acromegaly. 'Big-city' GH forms are associated with inappropriately low IGF-I levels. / Arosio, M.; Nissim, M.; Ballabio, M.; Orefice, R.; Bazzoni, N.; Faglia, G.

In: Acta Endocrinologica, Vol. 125, No. 2, 1991, p. 150-159.

Research output: Contribution to journalArticle

Arosio, M. ; Nissim, M. ; Ballabio, M. ; Orefice, R. ; Bazzoni, N. ; Faglia, G. / Size heterogeneity of circulating growth hormone in acromegaly. 'Big-city' GH forms are associated with inappropriately low IGF-I levels. In: Acta Endocrinologica. 1991 ; Vol. 125, No. 2. pp. 150-159.
@article{62c60bcdd28a4128b2b34c8f7454a9e0,
title = "Size heterogeneity of circulating growth hormone in acromegaly. 'Big-city' GH forms are associated with inappropriately low IGF-I levels",
abstract = "Circulating GH consists of several molecular size species with different biological activity. A reduced sensitivity of some monoclonal antibodies towards high molecular weight GH variants has been reported. The aim of the present work was to evaluate the molecular size species of circulating GH using Sephadex G-100 gel filtration chromatography in acromegalic patients and in normal subjects employing both RIA and an immunoradiometric assay for all GH determinations. In 6 normal subjects, studied under GHRH stimulation, little GH was 69.8 ± 6{\%} (mean ±SD), big GH (44 kD) 26.4 ± 6{\%} and big-big GH (>80 kD) 2.8 ± 4{\%}, in IRMA, with a good correspondence with RIA results (70.8 ± 8, 27.0 ± 4, and 3.2 ± 2{\%}, respectively). In 13 untreated acromegalic patients, studied in basal conditions, the little form constituted 76.2 ± 7{\%}, the big form 18.3 ± 4{\%}, which is significantly lower than in normals (p90 kD), not recognized by IRMA. All IRMA immunoreactivity eluted with a K(av) corresponding to 19-50 kD. In conclusion: a. the three main molecular size isomers of serum GH are similarly recognized by IRMA and RIA methods in normal subjects. b. in acromegaly, both quantitative and qualitative modifications of the GH chromatographic profile may be present. In particular, increased amounts of big-big forms, whether or not recognized by monoclonal antibodies, have been observed. Their lower bioactivity, suggested by the normal or lower than expected IGF-I levels, can account for the discrepancy between serum GH levels and the clinical picture or IGF-I levels sometimes observed in acromegaly.",
author = "M. Arosio and M. Nissim and M. Ballabio and R. Orefice and N. Bazzoni and G. Faglia",
year = "1991",
language = "English",
volume = "125",
pages = "150--159",
journal = "Acta Endocrinologica",
issn = "0001-5598",
publisher = "Munksgaard International Publishers",
number = "2",

}

TY - JOUR

T1 - Size heterogeneity of circulating growth hormone in acromegaly. 'Big-city' GH forms are associated with inappropriately low IGF-I levels

AU - Arosio, M.

AU - Nissim, M.

AU - Ballabio, M.

AU - Orefice, R.

AU - Bazzoni, N.

AU - Faglia, G.

PY - 1991

Y1 - 1991

N2 - Circulating GH consists of several molecular size species with different biological activity. A reduced sensitivity of some monoclonal antibodies towards high molecular weight GH variants has been reported. The aim of the present work was to evaluate the molecular size species of circulating GH using Sephadex G-100 gel filtration chromatography in acromegalic patients and in normal subjects employing both RIA and an immunoradiometric assay for all GH determinations. In 6 normal subjects, studied under GHRH stimulation, little GH was 69.8 ± 6% (mean ±SD), big GH (44 kD) 26.4 ± 6% and big-big GH (>80 kD) 2.8 ± 4%, in IRMA, with a good correspondence with RIA results (70.8 ± 8, 27.0 ± 4, and 3.2 ± 2%, respectively). In 13 untreated acromegalic patients, studied in basal conditions, the little form constituted 76.2 ± 7%, the big form 18.3 ± 4%, which is significantly lower than in normals (p90 kD), not recognized by IRMA. All IRMA immunoreactivity eluted with a K(av) corresponding to 19-50 kD. In conclusion: a. the three main molecular size isomers of serum GH are similarly recognized by IRMA and RIA methods in normal subjects. b. in acromegaly, both quantitative and qualitative modifications of the GH chromatographic profile may be present. In particular, increased amounts of big-big forms, whether or not recognized by monoclonal antibodies, have been observed. Their lower bioactivity, suggested by the normal or lower than expected IGF-I levels, can account for the discrepancy between serum GH levels and the clinical picture or IGF-I levels sometimes observed in acromegaly.

AB - Circulating GH consists of several molecular size species with different biological activity. A reduced sensitivity of some monoclonal antibodies towards high molecular weight GH variants has been reported. The aim of the present work was to evaluate the molecular size species of circulating GH using Sephadex G-100 gel filtration chromatography in acromegalic patients and in normal subjects employing both RIA and an immunoradiometric assay for all GH determinations. In 6 normal subjects, studied under GHRH stimulation, little GH was 69.8 ± 6% (mean ±SD), big GH (44 kD) 26.4 ± 6% and big-big GH (>80 kD) 2.8 ± 4%, in IRMA, with a good correspondence with RIA results (70.8 ± 8, 27.0 ± 4, and 3.2 ± 2%, respectively). In 13 untreated acromegalic patients, studied in basal conditions, the little form constituted 76.2 ± 7%, the big form 18.3 ± 4%, which is significantly lower than in normals (p90 kD), not recognized by IRMA. All IRMA immunoreactivity eluted with a K(av) corresponding to 19-50 kD. In conclusion: a. the three main molecular size isomers of serum GH are similarly recognized by IRMA and RIA methods in normal subjects. b. in acromegaly, both quantitative and qualitative modifications of the GH chromatographic profile may be present. In particular, increased amounts of big-big forms, whether or not recognized by monoclonal antibodies, have been observed. Their lower bioactivity, suggested by the normal or lower than expected IGF-I levels, can account for the discrepancy between serum GH levels and the clinical picture or IGF-I levels sometimes observed in acromegaly.

UR - http://www.scopus.com/inward/record.url?scp=0025836109&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025836109&partnerID=8YFLogxK

M3 - Article

C2 - 1897332

AN - SCOPUS:0025836109

VL - 125

SP - 150

EP - 159

JO - Acta Endocrinologica

JF - Acta Endocrinologica

SN - 0001-5598

IS - 2

ER -