Cortisol decreases IGF-I mRNA levels in human osteoblast-like cells.
Excess levels of glucocorticoids are known to cause osteoporosis. It is speculated that the effect of glucocorticoids could be mediated via regulation of IGF-I. The aims of the present study were to detect and quantify the expression of IGF-I and/or IGF-II mRNA transcripts in human osteoblast-like cells and to investigate whether glucocorticoids regulate the expression of IGF-I mRNA transcripts in human osteoblast-like cells. Cultures of human osteoblast-like cells from trabecular bone were established. The IGF-IA and IGF-IB transcripts were detected in human osteoblast-like cells from seven out of nine patients while the IGF-II transcript was detected in human osteoblast-like cells from eight out of nine patients, as determined by RT-PCR assays. Human osteoblast-like cells, as well as human muscle tissue, expressed approximately 1/10 of the IGF-I mRNA levels found in liver, as determined by RNase protection solution hybridization assay. The IGF-I mRNA levels did not decrease with age in the human osteoblast-like cells and no difference was seen between males and females. However, cortisol (10(-6) mol/l) decreased IGF-I mRNA levels. In summary, the present study has shown that human osteoblast-like cells express IGF-I and IGF-II mRNA transcripts and that cortisol down-regulates the IGF-I mRNA levels, indicating that some of the inhibitory effect of glucocorticoids on bone formation in humans is mediated via a reduced autocrine/paracrine expression of IGF-I.
Swolin
D
D
Department of Internal Medicine, University of Göteborg, Sweden.
Brantsing
C
C
Matejka
G
G
Ohlsson
C
C
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007223:Infant; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*
D017931:DNA Primers; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D006854:Hydrocortisone