Cortisol inhibits the synthesis of insulin-like growth factor-I in skeletal cells.
Abstract
Supraphysiological levels of cortisol inhibit bone cell replication and matrix synthesis, but its mechanism of action is unknown and could be secondary to an inhibition of local growth factor synthesis. These inhibitory effects of cortisol are the converse of the observed anabolic influences of the endogenously produced insulin-like growth factor-I (IGF-I); therefore, cortisol was examined for its effect on the production of IGF-I in osteoblast (Ob)- and fibroblast/preosteoblast-enriched cell cultures prepared from fetal rat parietal bone. Synthesis of IGF-I was monitored by Northern blot analysis to determine steady state IGF-I mRNA levels and by an IGF-I-specific RIA to quantitate polypeptide levels in acidified and fractionated culture medium. Cortisol at 100 nM decreased IGF-I transcript levels by 60% or more in Ob cultures within 6 h of treatment, and the concentration of immunoreactive IGF-I by 50% after 24 h; these effects were observed in the absence of a change in cellular DNA content. In Ob cultures, PTH at 10 nM increased IGF-I transcripts at 6 h and polypeptide levels at 24 h by 2.5- and 4.1-fold, respectively, and cortisol opposed this effect. The inhibitory effect of cortisol was not specific for the Ob cell population, since at 100 nM it also decreased IGF-I transcript and immunoreactive IGF-I levels in fibroblast/preosteoblast cultures and opposed the stimulation of IGF-I synthesis after treatment with 100 ng/ml GH. In conclusion, high levels of cortisol decrease skeletal IGF-I synthesis by reducing IGF-I transcript levels, and this effect probably contributes to the inhibitory influence of cortisol on bone formation.
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Glucocorticoids can inhibit osteoblast differentiation, attachment to bone matrix, and production of IGF-I.
“Glucocorticoids can also inhibit osteoblast differentiation (249 -251), osteoblast attachment to bone matrix (252), and osteoblast production of IGF-I (253).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [253]
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“attenuation of type I collagen synthesis and messenger RNA (mRNA) levels, decreased synthesis and activity of insulin-like growth factor 1 (IGF-1),((41,44,45)) and premature attenuation of the osteoblast cell cycle.”
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Self-citationInteraction between glucocorticoids and growth hormone
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“We would also like to thank the Department of Orthopedics, Sahlgrenska Hospital, and Dr Anders Nilsson for providing us with bone samples.”
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Systemic and local factors and the maintenance of bone quality
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- Authors
- MCCARTHY, T. L., CENTRELLA, M., & CANALIS, E.
- Affiliations
- Saint Francis Hospital & Medical Center (US)
- ORCID
- CANALIS, ERNESTO
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1990-03
- Volume
- 126
- Issue
- 3
- Pages
- 1569-1575
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W1981791036
- Cited by
- 204
- References
- 32
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 2 · 2016: 3 · 2015: 5 · 2014: 5 · 2013: 2 · 2012: 3
- FWCI
- 14.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Manitoba
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK042424, DK-42424)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-39201, AR 21707)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- cortisol, insulin-like growth factor I, osteoblasts, parietal bone, parathyroid hormone, growth hormone, IGF-I mRNA, bone formation
- MeSH terms
- Animals, Bone and Bones, Cells, Cultured, DNA, Hydrocortisone, Insulin-Like Growth Factor I, Nucleic Acid Hybridization, Parathyroid Hormone, RNA, Somatomedins, Transcription, Genetic, Blotting, Northern
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