Prednisolone reduces the ability of serum to activate the IGF1 receptor in vitro without affecting circulating total or free IGF1

Abstract

Objective: End-point bioassays based on thymidine or sulfate incorporation have demonstrated that glucocorticoid (GC) treatment inhibits serum IGF1 action, but the mechanism is unknown as serum IGF1 concentrations have been reported to either increase or remain unchanged. Aim: To investigate whether GC treatment affects the ability of serum to activate the IGF1 receptor (IGF1R) in vitro (i.e. bioactive IGF1), using a specific cell-based IGF1 kinase receptor activation assay. Subjects and methods: Twenty children with stable asthma (age 7.7-13.8 years) treated for 1 week with 5 mg prednisolone in a randomized, double-blind, placebo-controlled crossover study. Non-fasting serum samples were collected in the afternoon after each 7-day period and assayed for bioactive IGF1, free IGF1, total IGFs, IGF-binding proteins (IGFBPs), and insulin. Results: Prednisolone treatment reduced IGF1 bioactivity by 12.6% from 2.22G0.18 to 1.94 G0.15 mg/l (PZ0.01) compared with placebo. In contrast, no changes were observed for (mg/l; placebo vs prednisolone) total IGF1 (215G27 vs 212G24), free IGF1 (1.50G0.16 vs 1.43G0.17), total IGF2 (815G26 vs 800G31), IGFBP3 (3140G101 vs 3107G95), IGFBP2 (238G21 vs 220 G19), IGFBP1 (32G6 vs 42G10), or IGFBP1-bound IGF1 (24G5 vs 26G7). Insulin remained unchanged as did IGFBP levels as estimated by western ligand blotting. Prednisolone had no direct effects on IGF1R phosphorylation. Conclusions: Our study gives evidence that GC treatment induces a circulating substance that is able to inhibit IGF1R activation in vitro without affecting circulating free or total IGF1. This may be one of the mechanisms by which GC inhibits IGF1 action in vivo. However, the nature of this circulating substance remains to be identified.

Insulin-Like Growth Factor-1 Signaling in Lung Development and Inflammatory Lung Diseases

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L-thyroxine Stabilizes Autoimmune Inflammatory Process in Euthyroid Nongoitrous Children with Hashimoto’s Thyroiditis and Type 1 Diabetes Mellitus

“…Furthermore, subclinical or overt hypothyroidism occurred in 20% (69/330) of the children in our control group, a finding which suggests a higher risk of thyroid dysfunction progression in patients with autoimmune poliglandular syndrome type 3a than in the general pediatric population (7,8,9). According to one hypothesis, T4 administration causes a decrease in TSH level and this may indirectly lead to a decrease in magnitude of antigenic presentation (10).…”

Prednisolone but Not Infliximab Aggravates the Upregulated Hepatic Nitrogen Elimination in Patients with Active Inflammatory Bowel Disease

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