Transforming growth factor-alpha stimulates insulin-like growth factor binding protein-4 (IGFBP-4) expression and blocks follicle-stimulating hormone regulation of IGFBP-4 production in rat granulosa cells.
The ability of TGF-alpha to regulate insulin-like growth factor binding protein-4 (IGFBP-4), was investigated. Primary cultures of rat granulosa cells (GC) were grown in serum-free medium with rat (r) TGF-alpha and/or rFSH, and secreted IGFBP-4 protein and its steady state mRNA levels were measured by Western immunoblotting and Northern blotting, respectively. Control (untreated) cells secreted IGFBP-4 spontaneously, and the levels were increased by rTGF-alpha in a dose- and time-dependent manner. rTGF-alpha abolished FSH-induced IGFBP-4 protease activity and suppressed FSH-dependent effects on IGFBP-4 production. IGFBP-4 mRNA levels were decreased and increased by FSH and TGF-alpha, respectively, and TGF-alpha blocked the FSH effects. These results demonstrate that TGF-alpha is a potent stimulator of IGFBP-4 expression in rat GC and can overcome the regulatory effects of FSH on IGFBP-4 production. The consequence of these TGF-alpha effects is a marked, sustained increase in the levels of IGFBP-4 in the microenvironment.
Piferrer
F
F
Department of Reproductive Medicine, University of California, San Diego, La Jolla 92093-0674, USA.
Li
D
D
Shimasaki
S
S
Erickson
G F
GF
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005640:Follicle Stimulating Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000096:biosynthesis* / Q000187:drug effects*; D008666:Metalloendopeptidases / Q000187:drug effects / Q000378:metabolism; D011266:Pregnancy-Associated Plasma Protein-A; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
D018974:Insulin-Like Growth Factor Binding Protein 4; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D005640:Follicle Stimulating Hormone; D008666:Metalloendopeptidases; D011266:Pregnancy-Associated Plasma Protein-A