Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte
Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte
复制标题
DOI：
10.1242/dev.035238
复制
发表时间：
2009-06-01
期刊：
影响因子：
4.6
通讯作者：
Jaffe, Laurinda A.
中科院分区：
文献类型：
--
作者：
Norris, Rachael P.;Ratzan, William J.;Jaffe, Laurinda A.
哺乳动物卵母细胞在减数分裂前期被来自卵泡中周围体细胞的抑制信号阻滞。为了响应结合到体细胞上的受体的促黄体激素（LH），卵母细胞进入第二中期，在那里它可以受精。在这里，我们研究了体细胞如何调节卵母细胞的前体细胞到中期的转换，并显示体细胞的抑制信号是cGMP。在卵泡封闭的小鼠卵母细胞中使用FRET为基础的环核苷酸传感器，我们发现cGMP通过缝隙连接进入卵母细胞，在那里它抑制磷酸二酯酶PDE3A水解cAMP。这种抑制维持高浓度的cAMP，从而阻断减数分裂进程。LH通过降低体细胞中的cGMP水平（LH刺激后1小时从近似2 μ M降至近似80 nM）和关闭体细胞之间的间隙连接来逆转抑制信号。卵母细胞cGMP的减少（从1 μ M到40 nM）缓解了对PDE3A的抑制，使其活性增加了5倍。这导致卵母细胞cAMP减少（从接近700 nM到接近140 nM），导致减数分裂恢复。
Mammalian oocytes are arrested in meiotic prophase by an inhibitory signal from the surrounding somatic cells in the ovarian follicle. In response to luteinizing hormone (LH), which binds to receptors on the somatic cells, the oocyte proceeds to second metaphase, where it can be fertilized. Here we investigate how the somatic cells regulate the prophase-to-metaphase transition in the oocyte, and show that the inhibitory signal from the somatic cells is cGMP. Using FRET-based cyclic nucleotide sensors in follicle-enclosed mouse oocytes, we find that cGMP passes through gap junctions into the oocyte, where it inhibits the hydrolysis of cAMP by the phosphodiesterase PDE3A. This inhibition maintains a high concentration of cAMP and thus blocks meiotic progression. LH reverses the inhibitory signal by lowering cGMP levels in the somatic cells (from similar to 2 mu M to similar to 80 nM at 1 hour after LH stimulation) and by closing gap junctions between the somatic cells. The resulting decrease in oocyte cGMP ( from similar to 1 mu M to similar to 40 nM) relieves the inhibition of PDE3A, increasing its activity by similar to 5-fold. This causes a decrease in oocyte cAMP ( from similar to 700 nM to similar to 140 nM), leading to the resumption of meiosis.