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1: J Endocrinol. 2005 Oct;187(1):135-47.

Fibroblast growth factor (FGF) 2 and FGF9 mediate mesenchymal-epithelial
interactions of peritubular and Sertoli cells in the rat testis.

El Ramy R, Verot A, Mazaud S, Odet F, Magre S, Le Magueresse-Battistoni B.

Inserm U418/INRA UMR 1245, Hôpital Debrousse, 29 rue soeur Bouvier, 69322 Lyon
cedex 05, France.

The role of fibroblast growth factor (FGF) 2 and FGF9 as mediators of cell-cell
interactions between Sertoli cells (SCs) and peritubular cells (PCs) was
investigated. Using RT-PCR, we demonstrated that SCs and PCs recovered from
20-day-old rats expressed several of the seven FGF receptors (FGFRs), and more
specifically the FGFR1 IIIc. FGF2 and FGF9 did not elicit any morphological
changes in primary cultures of SCs, nor did they alter the number of SCs in
culture. By contrast, changes in shape were observed in FGF2- and FGF9-treated
PCs. In addition, FGF2 but not FGF9 enhanced significantly and dose-dependently
the number of PCs in culture, indicating that FGF2 was a survival factor for
these cells. It was also mitogenic because it enhanced the [3H]thymidine labeling
index in PCs. We next examined the effects of FGF2 and FGF9 in a coculture system
using 20-day-old rat SCs and PCs, and in an organotypic culture system using XY
rat embryonic gonads. In both models, FGF2 and FGF9 were found to promote
cellular interactions as evidenced by the extent of cellular reorganization in
the coculture system, and cord morphogenesis and growth in the organotypic
culture system. A key feature in SC-PC interactions is the synthesis and
remodeling of the basement membrane which is co-elaborated by the two cell types.
Since basement membrane homeostasis depends upon the coordinated activity of
proteinases and inhibitors, the proteinases and inhibitors produced by PCs and
SCs degrading or opposing degradation of the major components of the basement
membrane were further studied. Specifically, we monitored the metalloproteinases 
(MMP)-2 and -9 and the tissue inhibitors -1, -2 and -3, the plasminogen
activators (PAs) and the PA inhibitor-1, using zymography for the proteinases and
Western blots for the cognate inhibitors. Cocultures received FGF or an analog of
cAMP in order to prevent cellular reorganization. We found that FGF2 was unique
in inducing MMP-9 in coculture. Also, the enhanced levels of the PA inhibitor-1
and the 30 kDa band glycosylated form of tissue inhibitor-3 correlated with the
enhanced SC-PC reorganization. It was concluded that FGF2 and FGF9 are morphogens
for the formation of testicular cords.

PMID: 16214949 [PubMed - indexed for MEDLINE]

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