MAPK3/1 (ERK1/2) in Ovarian Granulosa Cells Are Essential for Female Fertility

被引:516
作者
Fan, Heng-Yu [1 ]
Liu, Zhilin [1 ]
Shimada, Masayuki [2 ]
Sterneck, Esta [3 ]
Johnson, Peter F. [4 ]
Hedrick, Stephen M. [5 ,6 ]
Richards, JoAnne S. [1 ]
机构
[1] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA
[2] Hiroshima Univ, Grad Sch Biosphere Sci, Dept Appl Anim Sci, Higashihiroshima 7398528, Japan
[3] NCI, Lab Cell & Dev Signaling, Ctr Canc Res, Frederick, MD 21702 USA
[4] NCI, Basic Res Lab, Ctr Canc Res, Frederick, MD 21702 USA
[5] Univ Calif San Diego, Dept Cell & Mol Biol, La Jolla, CA 92093 USA
[6] Univ Calif San Diego, Mol Biol Sect, Div Biol Sci, La Jolla, CA 92093 USA
基金
日本学术振兴会;
关键词
C/EBP-BETA; CUMULUS EXPANSION; KNOCKOUT MICE; MOUSE; EXPRESSION; OVULATION; FOLLICLE; PHOSPHORYLATION; COMMUNICATION; ACTIVATION;
D O I
10.1126/science.1171396
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
A surge of luteinizing hormone (LH) from the pituitary gland triggers ovulation, oocyte maturation, and luteinization for successful reproduction in mammals. Because the signaling molecules RAS and ERK1/2 ( extracellular signal-regulated kinases 1 and 2) are activated by an LH surge in granulosa cells of preovulatory follicles, we disrupted Erk1/2 in mouse granulosa cells and provide in vivo evidence that these kinases are necessary for LH-induced oocyte resumption of meiosis, ovulation, and luteinization. In addition, biochemical analyses and selected disruption of the Cebpb gene in granulosa cells demonstrate that C/EBPb (CCAAT/Enhancer-binding protein-beta) is a critical downstream mediator of ERK1/2 activation. Thus, ERK1/2 and C/EBPb constitute an in vivo LH-regulated signaling pathway that controls ovulation- and luteinization-related events.
引用
收藏
页码:938 / 941
页数:4
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