Mette Bjerre

Effects of prednisolone on serum and tissue fluid IGF-I receptor activation and post-receptor signaling in humans

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Effects of prednisolone on serum and tissue fluid IGF-I receptor activation and post-receptor signaling in humans. / Ramshanker, Nilani; Aagaard, Maiken; Hjortebjerg, Rikke; Voss, Thomas Schmidt; Møller, Niels; Jørgensen, Jens Otto Lunde; Jessen, Niels; Bjerring, Peter; Magnusson, Nils Erik; Bjerre, Mette; Oxvig, Claus; Frystyk, Jan.

I: Journal of Clinical Endocrinology and Metabolism, Bind 102, Nr. 11, 11.2017, s. 4031-4040.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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Ramshanker, Nilani o.a.. "Effects of prednisolone on serum and tissue fluid IGF-I receptor activation and post-receptor signaling in humans". Journal of Clinical Endocrinology and Metabolism. 2017, 102(11). 4031-4040. https://doi.org/10.1210/jc.2017-00696

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Ramshanker, Nilani ; Aagaard, Maiken ; Hjortebjerg, Rikke ; Voss, Thomas Schmidt ; Møller, Niels ; Jørgensen, Jens Otto Lunde ; Jessen, Niels ; Bjerring, Peter ; Magnusson, Nils Erik ; Bjerre, Mette ; Oxvig, Claus ; Frystyk, Jan. / Effects of prednisolone on serum and tissue fluid IGF-I receptor activation and post-receptor signaling in humans. I: Journal of Clinical Endocrinology and Metabolism. 2017 ; Bind 102, Nr. 11. s. 4031-4040.

Bibtex

@article{a5a8588dd1dc419193f73f6ec97e9260,
title = "Effects of prednisolone on serum and tissue fluid IGF-I receptor activation and post-receptor signaling in humans",
abstract = "Context: Short-term glucocorticoid exposure increases serum IGF-I concentrations, but antagonizes IGF-I tissue signaling. The underlying mechanisms remain unknown.Objective: To identify at which levels glucocorticoid inhibits IGF-I signaling.Design and methods: Nineteen healthy males received prednisolone (37.5 mg daily) and placebo for 5 days in a randomized, double-blinded, placebo-controlled cross-over study. Serum was collected on day 1, 3 and 5, abdominal skin suction blister fluid (SBF; ≈interstitial fluid) on day 5 (n=9) together with muscle biopsies (n=19). The ability of serum and SBF to activate the IGF-I receptor (IGF-IR) (bioactive IGF) and its down-stream signaling proteins (IRS-1, Akt and mTOR) were assessed using IGF-IR transfected cells.Results: Prednisolone increased IGF-I concentrations and bioactive IGF in serum (P≤0.001), but not in SBF, which when compared to serum contained less bioactive IGF (≈28%) after prednisolone (P<0.05). This observation was unexplained by SBF concentrations of IGFs and IGF-binding proteins (IGFBPs) -1 to -3. However, following prednisolone treatment, SBF contained less IGFBP-4 fragments (P<0.05) generated by pregnancy-associated plasma protein-A (PAPP-A). Concomitantly, prednisolone increased SBF levels of stanniocalcin-2 (STC2) (P=0.02) when compared to serum. STC2 blocks PAPP-A from cleaving IGFBP-4. Finally, prednisolone suppressed post-IGF-IR signaling pathways at the level of IRS-1(P<0.05), but did not change skeletal muscle IGF-IR, IGF-I or STC2 mRNA.Conclusion: Prednisolone increased IGF-I concentrations and IGF bioactivity in serum, but not in tissue fluid. The latter may relate to a STC2-mediated inhibition of PAPP-A in tissue fluids. Furthermore, prednisolone induced post-IGF-IR resistance. Thus, glucocorticoid may exert distinct, compartment-specific effects on IGF-action.",
keywords = "Journal Article",
author = "Nilani Ramshanker and Maiken Aagaard and Rikke Hjortebjerg and Voss, {Thomas Schmidt} and Niels M{\o}ller and J{\o}rgensen, {Jens Otto Lunde} and Niels Jessen and Peter Bjerring and Magnusson, {Nils Erik} and Mette Bjerre and Claus Oxvig and Jan Frystyk",
year = "2017",
month = nov,
doi = "10.1210/jc.2017-00696",
language = "English",
volume = "102",
pages = "4031--4040",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Oxford University Press",
number = "11",

}

RIS

TY - JOUR

T1 - Effects of prednisolone on serum and tissue fluid IGF-I receptor activation and post-receptor signaling in humans

AU - Ramshanker, Nilani

AU - Aagaard, Maiken

AU - Hjortebjerg, Rikke

AU - Voss, Thomas Schmidt

AU - Møller, Niels

AU - Jørgensen, Jens Otto Lunde

AU - Jessen, Niels

AU - Bjerring, Peter

AU - Magnusson, Nils Erik

AU - Bjerre, Mette

AU - Oxvig, Claus

AU - Frystyk, Jan

PY - 2017/11

Y1 - 2017/11

N2 - Context: Short-term glucocorticoid exposure increases serum IGF-I concentrations, but antagonizes IGF-I tissue signaling. The underlying mechanisms remain unknown.Objective: To identify at which levels glucocorticoid inhibits IGF-I signaling.Design and methods: Nineteen healthy males received prednisolone (37.5 mg daily) and placebo for 5 days in a randomized, double-blinded, placebo-controlled cross-over study. Serum was collected on day 1, 3 and 5, abdominal skin suction blister fluid (SBF; ≈interstitial fluid) on day 5 (n=9) together with muscle biopsies (n=19). The ability of serum and SBF to activate the IGF-I receptor (IGF-IR) (bioactive IGF) and its down-stream signaling proteins (IRS-1, Akt and mTOR) were assessed using IGF-IR transfected cells.Results: Prednisolone increased IGF-I concentrations and bioactive IGF in serum (P≤0.001), but not in SBF, which when compared to serum contained less bioactive IGF (≈28%) after prednisolone (P<0.05). This observation was unexplained by SBF concentrations of IGFs and IGF-binding proteins (IGFBPs) -1 to -3. However, following prednisolone treatment, SBF contained less IGFBP-4 fragments (P<0.05) generated by pregnancy-associated plasma protein-A (PAPP-A). Concomitantly, prednisolone increased SBF levels of stanniocalcin-2 (STC2) (P=0.02) when compared to serum. STC2 blocks PAPP-A from cleaving IGFBP-4. Finally, prednisolone suppressed post-IGF-IR signaling pathways at the level of IRS-1(P<0.05), but did not change skeletal muscle IGF-IR, IGF-I or STC2 mRNA.Conclusion: Prednisolone increased IGF-I concentrations and IGF bioactivity in serum, but not in tissue fluid. The latter may relate to a STC2-mediated inhibition of PAPP-A in tissue fluids. Furthermore, prednisolone induced post-IGF-IR resistance. Thus, glucocorticoid may exert distinct, compartment-specific effects on IGF-action.

AB - Context: Short-term glucocorticoid exposure increases serum IGF-I concentrations, but antagonizes IGF-I tissue signaling. The underlying mechanisms remain unknown.Objective: To identify at which levels glucocorticoid inhibits IGF-I signaling.Design and methods: Nineteen healthy males received prednisolone (37.5 mg daily) and placebo for 5 days in a randomized, double-blinded, placebo-controlled cross-over study. Serum was collected on day 1, 3 and 5, abdominal skin suction blister fluid (SBF; ≈interstitial fluid) on day 5 (n=9) together with muscle biopsies (n=19). The ability of serum and SBF to activate the IGF-I receptor (IGF-IR) (bioactive IGF) and its down-stream signaling proteins (IRS-1, Akt and mTOR) were assessed using IGF-IR transfected cells.Results: Prednisolone increased IGF-I concentrations and bioactive IGF in serum (P≤0.001), but not in SBF, which when compared to serum contained less bioactive IGF (≈28%) after prednisolone (P<0.05). This observation was unexplained by SBF concentrations of IGFs and IGF-binding proteins (IGFBPs) -1 to -3. However, following prednisolone treatment, SBF contained less IGFBP-4 fragments (P<0.05) generated by pregnancy-associated plasma protein-A (PAPP-A). Concomitantly, prednisolone increased SBF levels of stanniocalcin-2 (STC2) (P=0.02) when compared to serum. STC2 blocks PAPP-A from cleaving IGFBP-4. Finally, prednisolone suppressed post-IGF-IR signaling pathways at the level of IRS-1(P<0.05), but did not change skeletal muscle IGF-IR, IGF-I or STC2 mRNA.Conclusion: Prednisolone increased IGF-I concentrations and IGF bioactivity in serum, but not in tissue fluid. The latter may relate to a STC2-mediated inhibition of PAPP-A in tissue fluids. Furthermore, prednisolone induced post-IGF-IR resistance. Thus, glucocorticoid may exert distinct, compartment-specific effects on IGF-action.

KW - Journal Article

U2 - 10.1210/jc.2017-00696

DO - 10.1210/jc.2017-00696

M3 - Journal article

C2 - 28945869

VL - 102

SP - 4031

EP - 4040

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 11

ER -