Synergistic effects of activin and FSH on hyperphosphorylation of Rb and G1/S transition in rat primary granulosa cells.
Activin is produced in mammalian ovarian follicles and is known to function as a paracrine as well as autocrine factor for folliculogenesis and oogenesis. We investigated the functional mechanism of activin using a hormone-supplemented serum-free culture system of granulosa cells isolated from diethylstilbestrol (DES)-primed 21-day-old rats. Recombinant human-activin A appeared to induce CycD2 and to act synergistically with FSH to promote G1/S transition and cell proliferation starting from 12h after stimulation, accompanied by an increase of the hyperphosphorylated retinoblastoma protein (ppRb). Cells from unprimed rats gave similar results. FSH, in contrast, showed no CycD2-inducing activity, but turned out to modulate CycD2/cdk4 complex formation and enhance ppRb formation in conjunction with activin. These findings showed that the induction of CycD2 by activin and the synergistic effect of activin with FSH on ppRb formation play important roles in promoting G1/S transition in rat primary granulosa cells.
Ogawa
Takuya
T
Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0101, Japan.
Yogo
Keiichiro
K
Ishida
Norihiro
N
Takeya
Tatsuo
T
D028341:Activins / Q000494:pharmacology*; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D056742:Cyclin D2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004054:Diethylstilbestrol / Q000494:pharmacology; D004357:Drug Synergism; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D028322:Inhibin-beta Subunits / Q000494:pharmacology*; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D016160:Retinoblastoma Protein / Q000378:metabolism*
C080336:CCND2 protein, human; C486197:Ccnd2 protein, rat; D016895:Culture Media, Serum-Free; D056742:Cyclin D2; D016213:Cyclins; D004968:Estrogens, Non-Steroidal; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; C422405:activin A; D028341:Activins; D004054:Diethylstilbestrol; D005640:Follicle Stimulating Hormone; D028322:Inhibin-beta Subunits; C495900:CDK4 protein, human; C495903:Cdk4 protein, rat; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases