磷酸二酯酶在卵母细胞成熟中的作用

Role of Cyclic Nucleotide Phosphodiesterases in Oocyte Maturation

卵母细胞成熟是一个包括内分泌、旁分泌以及自分泌的复杂过程,所涉及的信号通路最终都要转化为对环核苷酸的调控。磷酸二酯酶(phosphodiesterase,PDE)是一类降解cAMP并使之失活的酶,在卵巢中存在区域化分布。其中PDE3主要分布于卵母细胞,而PDE4分布于颗粒细胞。体内外研究证实,抑制哺乳动物卵母细胞PDE3活性能阻断减数分裂,活性PDE3在两栖动物中的表达能诱导减数分裂重启,程度与孕酮/胰岛素诱导的相近。PI-3K/Akt信号通路参与IGF1/胰岛素诱导的爪蟾卵母细胞成熟,而在孕酮诱导的成熟中不起作用。PDE3作为PKB\Akt激酶的下游因子,通过调节胞内cAMP水平达到对卵母细胞成熟的调控。此外,哺乳动物卵母细胞中也可能存在类似的信号通路。因此,PDE3在调控两栖类和哺乳动物减数分裂信号通路中扮演重要角色。掌握PDE3的调控方式便于人们更好的了解诱导卵母细胞成熟的信号通路。

Oocyte maturation is a complex set of endocrine, paracrine, and autocrine inputs that are translated into the regulation of cyclic nucleotide levels. Phosphodiesteras （PDEs）, the enzymes that degrade and inactivate cAMP, show compartmentalized expression in ovary..The PDE3 is mainly expressed in the oocytes while PDE4s are expressed in granulosa cells. Inhibition of the mammalian oocyte PDE3 completely blocked meiosis in vitro and in vivo, expression of an active PDE3A in Xenopus oocyte causes resumption of meiosis to the same extent as progesterone or insulin. PI-3K/Akt pathway mediates IGF-1/insulin but not progesterone-induced oocyte maturation. PDE3, as downstream factor of PKB/Akt, mediates oocyte maturation by controlling cAMP level. Furthermore, a similar regulatory module may exist in mammalian oocytes. Thus, PDE3 plays an essential role in the signaling pathway that controls resumption of meiosis in amphibians and mammals. Understanding the regulation of this enzyme may shed some light on the signals that trigger oocyte maturation.