Fibroblast growth factor stimulates the gene expression and production of tissue inhibitor of metalloproteinase-1 in bovine granulosa cells.
The hormonal control of tissue inhibitor of metalloproteinase-1 (TIMP-1) gene expression and production by growth factors, gonadotrophins, and serum factors in cultured bovine granulosa cells (BGC) were investigated. Confluent cultures of BGC were exposed to various factors in a defined medium and levels of TIMP-1 in the conditioned medium were determined by enzyme immunoassay. Basic fibroblast growth factor (bFGF) and acidic fibroblast growth factor (aFGF) showed potent stimulation of cell proliferation and TIMP-1 production by BGC, while insulin stimulated growth but not TIMP-1 production. Basic FGF stimulated TIMP-1 production and BGC cell proliferation in a dose-dependent manner. A time course of TIMP-1 production showed substantially increased levels between 18 and 24 h in both control and bFGF-stimulated BGC cultures with bFGF-stimulated cultures having markedly higher TIMP-1 production at all time points. Consistent with the TIMP-1 production data, bFGF and aFGF increased the expression of TIMP-1 mRNA as determined by northern blot analysis, while insulin, inhibited TIMP-1 mRNA levels. These results indicate that FGF-induced TIMP-1 production by BGC may support bovine embryo development in vitro.
Research Institute for the Functional Peptides, Yamagata, Japan.
H
H
Hoshi
S
S
Konno
M
M
Kikuchi
Y
Y
Sendai
T
T
Satoh
D000818:Animals; D015152:Blotting, Northern; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007328:Insulin / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D007328:Insulin; D011480:Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D008666:Metalloendopeptidases