Abnormal GH receptor signaling in children with idiopathic short stature

Mariacarolina Salerno, Barbara Balestrieri, Eliana Matrecano, Annunziata Officioso, Ronald (Ron) Rosenfeld, Salvatore Di Maio, Giorgia Fimiani, Matilde Valeria Ursini, Claudio Pignata

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Peripheral GH insensitivity may underlie idiopathic short stature in children. As the clinical and biochemical hallmarks of partial GH insensitivity have not yet been clearly elucidated, the identification of such patients is still difficult. We integrated functional, biochemical, and molecular studies to define the more reliable marker(s) of GH insensitivity. In particular, we measured GH receptor transducing properties through GH-induced protein tyrosine phosphorylation in patients' peripheral blood mononuclear cells and performed direct sequencing analysis of GH receptor-coding exons. Five of 14 idiopathic short stature patients with low basal IGF-I levels showed low or absent IGF-I increment after 4 d of GH administration. However, a prolonged GH stimulation induced in 3 of them an increase in IGF-140% above the baseline value. The IGF-binding protein-3 behavior paralleled that of IGF-I. The 2 GH-unresponsive subjects showed an abnormal tyrosine phosphorylation pattern after GH challenge. Sequence analysis of the GH receptor gene revealed a heterozygous mutation resulting in an Arg to Cys change (R161C) in exon 6 in only 1 patient, who had normal GH receptor responsiveness. Our findings indicate that abnormal GH receptor signaling may underlie idiopathic short stature even in the absence of GH receptor mutations. Thus, combining the 4-dIGF-I generation test and the analysis of GH-induced protein tyrosine phosphorylation is a useful tool to help identify idiopathic short stature patients with partial GH insensitivity.

Original languageEnglish (US)
Pages (from-to)3882-3888
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume86
Issue number8
DOIs
StatePublished - 2001

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Phosphorylation
Insulin-Like Growth Factor I
Tyrosine
Exons
Insulin-Like Growth Factor Binding Protein 3
Proteins
Blood
Genes
Mutation
Sequence Analysis
Blood Cells

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Salerno, M., Balestrieri, B., Matrecano, E., Officioso, A., Rosenfeld, R. R., Di Maio, S., ... Pignata, C. (2001). Abnormal GH receptor signaling in children with idiopathic short stature. Journal of Clinical Endocrinology and Metabolism, 86(8), 3882-3888. https://doi.org/10.1210/jc.86.8.3882

Abnormal GH receptor signaling in children with idiopathic short stature. / Salerno, Mariacarolina; Balestrieri, Barbara; Matrecano, Eliana; Officioso, Annunziata; Rosenfeld, Ronald (Ron); Di Maio, Salvatore; Fimiani, Giorgia; Ursini, Matilde Valeria; Pignata, Claudio.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 86, No. 8, 2001, p. 3882-3888.

Research output: Contribution to journalArticle

Salerno, M, Balestrieri, B, Matrecano, E, Officioso, A, Rosenfeld, RR, Di Maio, S, Fimiani, G, Ursini, MV & Pignata, C 2001, 'Abnormal GH receptor signaling in children with idiopathic short stature', Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 8, pp. 3882-3888. https://doi.org/10.1210/jc.86.8.3882
Salerno M, Balestrieri B, Matrecano E, Officioso A, Rosenfeld RR, Di Maio S et al. Abnormal GH receptor signaling in children with idiopathic short stature. Journal of Clinical Endocrinology and Metabolism. 2001;86(8):3882-3888. https://doi.org/10.1210/jc.86.8.3882
Salerno, Mariacarolina ; Balestrieri, Barbara ; Matrecano, Eliana ; Officioso, Annunziata ; Rosenfeld, Ronald (Ron) ; Di Maio, Salvatore ; Fimiani, Giorgia ; Ursini, Matilde Valeria ; Pignata, Claudio. / Abnormal GH receptor signaling in children with idiopathic short stature. In: Journal of Clinical Endocrinology and Metabolism. 2001 ; Vol. 86, No. 8. pp. 3882-3888.
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