IGF-I and not IGF-II expression is regulated by glucocorticoids in human fetal epiphyseal chondrocytes.
OBJECTIVE
To elucidate the involvement of IGF axis components and the potential effects of glucocorticoids (GCs) in human fetal growth regulation.


METHODS
We studied the regulation by dexamethasone (Dx) and IGF-I of proliferation and IGF axis components and matrix protein gene expression in human fetal epiphyseal chondrocytes.


RESULTS
High Dx concentration (10(-7)-10(-6)M) inhibited (3)H-thymidine incorporation, mifepristone (MF) 10(-6)M limited inhibition by Dx, and IGF-I (100 ng/ml) significantly stimulated proliferation and completely opposed inhibition by Dx. Dx dose-dependently (10(-9)-10(-6)M) inhibited IGF-I, IGFBP3 and SOX9 gene expression and expression of GHR, COL2A1 and aggrecan from 10(-7)M to 10(-6)M whereas it stimulated IGF-IR expression. By contrast, Dx had no significant effect on IGF-II expression. IGF-I stimulated IGF-I, IGFBP3, SOX9, COL2A1 and aggrecan expression whereas it inhibited IGF-IR expression. IGF-I could oppose COL2A1 and aggrecan gene expression inhibition by Dx.


CONCLUSIONS
We demonstrated for the first time by real-time quantitative PCR that human fetal epiphyseal chondrocytes expressed IGF axis components, such as IGF-I, IGF-II, IGFBP3, IGF-IR and GHR and SOX9, COL2A1 and aggrecan, and that their expression was regulated by Dx and IGF-I. Among IGFs, IGF-I and not IGF-II expression was demonstrated to be down-regulated by GCs whereas IGF-I expression was up-regulated by itself.
Fernandez-Cancio
M
M
Pediatric Endocrinology Research Unit, Hospital Vall d'Hebron, Autonomous University, Barcelona, Spain. mfernand@ir.vhebron.net
Esteban
C
C
Carrascosa
A
A
Toran
N
N
Andaluz
P
P
Audi
L
L
D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000166:cytology; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology*; D006132:Growth Plate / Q000166:cytology* / Q000196:embryology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male; D015735:Mifepristone / Q000494:pharmacology
D016326:Extracellular Matrix Proteins; D005938:Glucocorticoids; D015735:Mifepristone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D003907:Dexamethasone