Generation of growth hormone binding protein by avian growth plate chondrocytes is dependent on cell differentiation

Efrat Monsonego, William R. Baumbach, Irina Lavelin, Arieh Gertler, Shmuel Hurwitz, Mark Pines*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Growth hormone receptor (GH-R) gene expression was evaluated in avian growth-plates in situ and in cultured chondrocytes. In the epiphyseal growth-plate, chondrocytes at different stages of differentiation located at the proliferative and upper hypertrophic zones express the GH-R gene. In culture, addition of ascorbic acid facilitated chondrocyte differentiation as evaluated by decrease in collagen type II gene expression and increase in alkaline phosphatase activity and osteopontin gene expression. Both the ascorbic acid-treated and untreated chondrocytes expressed the gene coding for the chicken growth hormone receptor (cGH-R), but only the undifferentiated cells were capable of binding the hormone. This reduction in GH-binding resulted in alteration in GH-dependent regulation of the GH-R gene expression: only the undifferentiated chondrocytes responded to chicken GH (cGH) by down-regulation of the cGH-R gene expression. Chondrocyte differentiation induced by either ascorbic acid or retinoic acid was associated with the appearance of two growth hormone binding-proteins (GHBPs) in the culture medium with estimated MWs of 32 and 70 kDa, respectively. These GHBPs differ in their MW from the major GHBP found in chicken plasma. Chondrocyte GHBPs specifically bind [125I]cGH, which can be displaced by an excess of unlabeled cGH. The differentiation-dependent increase in the 70 kDa GHBP was observed also using specific chicken GHBP antiserum. Our data suggest that the reduction of the differentiated chondrocytes response to GH is due to differentiation-dependent loss of the extracellular domain of the GH-R, resulting in a lack of functional receptors on the cell surface and generation of GHBP.

Original languageAmerican English
Pages (from-to)1-10
Number of pages10
JournalMolecular and Cellular Endocrinology
Volume135
Issue number1
DOIs
StatePublished - 30 Nov 1997
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by a grant from BARD, the United States–Israel Binational Agricultural Research and Development Fund (US-2627-95C). A contribution from the Agricultural Research Organization, The Volcani Center, Bet Dagan, Israel (No. 2009-E, 1996 series) is also acknowledged.

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