Effect of growth hormone and insulin-like growth factor I (IGF-I) on the expression of IGF-I messenger ribonucleic acid and peptide in rat tibial growth plate and articular chondrocytes in vivo.
Conflicting data exist as to whether insulin-like growth factor I (IGF-I) messenger RNA (mRNA) and peptide are expressed within chondrocytes. This question is pertinent to the mode of GH action on longitudinal bone growth. We have, therefore, investigated this issue in normal rats and in hypophysectomized rats treated for 24 h with GH or IGF-I using in situ hybridization and immunohistochemistry. Serum IGF-I, body weight, and tibial growth plate, but not articular cartilage, height increased with both treatments. Both IGF-I mRNA and IGF-I immunoreactivity occurred in all chondrocyte layers of growth plate and articular cartilage. The percentage of cells with IGF-I mRNA correlated well with IGF-I immunoreactivity under all experimental conditions. In normal rats, IGF-I expression was highest in the upper hypertrophic zone in growth plate (68-71%) and articular cartilage (32-34%). Hypophysectomy, GH, or IGF-I did not significantly affect this percentage. In the stem cell and proliferative and lower hypertrophic zones of growth plate, hypophysectomy dramatically reduced the percentage of labeled chondrocytes, and GH restored it. IGF-I increased IGF-I mRNA and immunoreactivity only in the proliferative zone. In articular cartilage, both remained unchanged under all experimental conditions. Together with our previous finding that GH infusion of hypophysectomized rats enhances chondrocyte maturation at all differentiation stages, the present results are compatible with the idea that IGF-I produced by all chondrocyte layers under the influence of GH mediates chondrocyte maturation and thus longitudinal bone growth in an autocrine/paracrine manner.
Division of Neuroendocrinology, Institute of Anatomy, University of Zurich, Switzerland. reinecke@anatom.unizh.ch
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M
Reinecke
A C
AC
Schmid
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B
Heyberger-Meyer
E B
EB
Hunziker
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J
Zapf
D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D006132:Growth Plate / Q000378:metabolism*; D019382:Human Growth Hormone / Q000494:pharmacology*; D007016:Hypophysectomy; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013977:Tibia
D012333:RNA, Messenger; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I