Glucocorticoid regulation of insulin-like growth factor-binding protein-3

Endocrinology
B C VillafuerteL S Phillips

Abstract

Short stature and decreased growth velocity are prominent features of endogenous and pharmacological glucocorticoid excess in children. Underlying processes may involve direct cellular effects or defective generation of insulin-like growth factors (IGFs) and/or IGF-binding proteins (IGFBPs), which modulate IGF-stimulated events and regulate growth. To evaluate potential mechanisms, we investigated the impact of dexamethasone (dex) on hepatic expression of IGFBP-3, the major carrier protein for IGFs. Using cocultured hepatic parenchymal and nonparenchymal cells, dex at 10(-8) and 10(-6) M decreased IGFBP-3 secretion by 67 +/- 9% and 73 +/- 9%, respectively (both P < 0.05 vs. no dex). In a separate experiment, IGFBP-3 messenger RNA (mRNA) expression was decreased by 84 +/- 2% and 75 +/- 2% (both P < 0.05 vs. no dex). In combined studies, levels of IGFBP-3 protein in conditioned medium were strongly correlated with the abundance of IGFBP-3 mRNA (r = 0.75; P < 0.01), consistent with regulation at a pretranslational level. After inhibition of transcription, levels of IGFBP-3 mRNA decreased 85% and 86% over 24 h in cells cultured in 10(-6) M and no dex, respectively; the t1/2 was 13.6 h at 10(-6) M and 12.6 h with no dex, indicating ...Continue Reading

Citations

May 29, 2001·Molecular Pathology : MP·J G ScharfG Ramadori
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May 1, 2018·Frontiers in Bioengineering and Biotechnology·Hanaa Esa AlkharobiReem El-Gendy
Feb 10, 1999·The American Journal of Physiology·D G BurrinX Chang
Feb 21, 1997·The Journal of Biological Chemistry·B C VillafuerteL S Phillips
Nov 5, 1997·General and Comparative Endocrinology·Y Takagi, B T Björnsson
Nov 4, 2021·Journal of Applied Animal Welfare Science : JAAWS·Christian ManteuffelElisa Wirthgen

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