H. Hoshi et al., FIBROBLAST GROWTH-FACTOR STIMULATES THE GENE-EXPRESSION AND PRODUCTION OF TISSUE INHIBITOR OF METALLOPROTEINASE-1 IN BOVINE GRANULOSA-CELLS, In vitro cellular & developmental biology. Animal, 31(7), 1995, pp. 559-563
The hormonal control of tissue inhibitor of metalloproteinase-1 (TIMP-
1) gene expression and production by growth factors, gonadotrophins, a
nd serum factors in cultured bovine granulosa cells (BGC) were investi
gated. Confluent cultures of BGC were exposed to various factors in a
defined medium and levels of TIMP-1 in the conditioned medium were det
ermined by enzyme immunoassay. Basic fibroblast growth factor (bFGF) a
nd acidic fibroblast growth factor (aFGF) showed potent stimulation of
cell proliferation and TIMP-1 production by BGC, while insulin stimul
ated growth but not TIMP-1 production. Basic FGF stimulated TIMP-1 pro
duction and BGC cell proliferation in a dose-dependent manner. A time
course of TIMP-1 production showed substantially increased levels betw
een 18 and 24 h in both control and bFGF-stimulated BGC cultures with
bFGF-stimulated cultures having markedly higher TIMP-1 production at a
ll time points. Consistent with the TIMP-1 production data, bFGF and a
FGF increased the expression of TIMP-1 mRNA as determined by northern
blot analysis, while insulin, inhibited TIMP-1 mRNA levels. These resu
lts indicate that FGF-induced TIMP-1 production by BGC may support bov
ine embryo development in vitro.