Luteinizing hormone signaling phosphorylates and activates the cyclic GMP phosphodiesterase PDE5 in mouse ovarian follicles, contributing an additional component to the hormonally induced decrease in cyclic GMP that reinitiates meiosis.
Luteinizing hormone signaling phosphorylates and activates the cyclic GMP phosphodiesterase PDE5 in mouse ovarian follicles, contributing an additional component to the hormonally induced decrease in cyclic GMP that reinitiates meiosis.
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DOI：
10.1016/j.ydbio.2018.01.008
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发表时间：
2018-03-01
影响因子：
2.7
通讯作者：
Jaffe LA
中科院分区：
文献类型：
--
作者：
Egbert JR;Yee SP;Jaffe LA
在出生前，哺乳动物卵泡内的卵母细胞开始减数分裂，但随后停滞在前期直到青春期，在每个生殖周期，一个或多个卵泡被黄体生成素(LH)刺激以恢复减数分裂，为受精做准备。在排卵前卵泡内，颗粒细胞产生高水平的cGMP，cGMP扩散到卵母细胞中以维持减数分裂停滞。黄体生成素信号通过迅速降低卵泡和卵母细胞中cGMP的水平来重新启动减数分裂。这种下降的一部分是通过去磷酸化和失活NPR2鸟苷酸环化酶对黄体生成素的反应，但其余的cGMP下降的机制尚不清楚。至少有一种cGMP磷酸二酯酶PDE5被黄体生成素信号激活，这可能有助于降低cGMP。当PDE5在丝氨酸92上磷酸化时，显示出更高的cGMP水解酶活性，我们最近证明，黄体生成素信号使该丝氨酸上的PDE5磷酸化，并增加其在大鼠卵泡中的活性。为了测试这一机制在多大程度上有助于重新启动减数分裂的cGMP减少，我们产生了一个小鼠系，其中丝氨酸92突变为丙氨酸(PDE5-S92A)，因此它不能被磷酸化。在这里，我们证明了PDE5的磷酸化是黄体生成素诱导的cGMP水解酶活性增加所必需的，但这种增加对黄体生成素诱导的小鼠卵泡中cGMP的减少只有轻微的影响，并且不影响减数分裂恢复的时间。虽然我们发现PDE5的激活是导致cGMP减少的机制之一，但这些结果表明另一种cGMP磷酸二酯酶也被黄体生成素信号激活。
Prior to birth, oocytes within mammalian ovarian follicles initiate meiosis, but then arrest in prophase until puberty, when with each reproductive cycle, one or more follicles are stimulated by luteinizing hormone (LH) to resume meiosis in preparation for fertilization. Within preovulatory follicles, granulosa cells produce high levels of cGMP, which diffuses into the oocyte to maintain meiotic arrest. LH signaling restarts meiosis by rapidly lowering the levels of cGMP in the follicle and oocyte. Part of this decrease is mediated by the dephosphorylation and inactivation the NPR2 guanylyl cyclase in response to LH, but the mechanism for the remainder of the cGMP decrease is unknown. At least one cGMP phosphodiesterase, PDE5, is activated by LH signaling, which would contribute to lowering cGMP. PDE5 exhibits increased cGMP-hydrolytic activity when phosphorylated on serine 92, and we recently demonstrated that LH signaling phosphorylates PDE5 on this serine and increases its activity in rat follicles. To test the extent to which this mechanism contributes to the cGMP decrease that restarts meiosis, we generated a mouse line in which serine 92 was mutated to alanine (Pde5-S92A), such that it cannot be phosphorylated. Here we show that PDE5 phosphorylation is required for the LH-induced increase in cGMP-hydrolytic activity, but that this increase has only a modest effect on the LH-induced cGMP decrease in mouse follicles, and does not affect the timing of meiotic resumption. Though we show that the activation of PDE5 is among the mechanisms contributing to the cGMP decrease, these results suggest that another cGMP phosphodiesterase is also activated by LH signaling.
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影响因子：
4.6
作者：
Norris, Rachael P.;Freudzon, Marina;Mehlmann, Lisa M.;Cowan, Ann E.;Simon, Alexander M.;Paul, David L.;Lampe, Paul D.;Jaffe, Laurinda A.
通讯作者：
Jaffe, Laurinda A.
影响因子：
2.5
作者：
Downs, Stephen M.
通讯作者：
Downs, Stephen M.
DOI：
10.1083/jcb.200211041
发表时间：
2003-03-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mullershausen F;Friebe A;Feil R;Thompson WJ;Hofmann F;Koesling D
通讯作者：
Koesling D
影响因子：
20.1
作者：
Goetz, Konrad R.;Sprenger, Julia U.;Nikolaev, Viacheslav O.
通讯作者：
Nikolaev, Viacheslav O.
影响因子：
4.6
作者：
Norris, Rachael P.;Ratzan, William J.;Jaffe, Laurinda A.
通讯作者：
Jaffe, Laurinda A.