Thomas Peter
Marine Science Institute, University of Texas at Austin, 750 Channel View Drive, Port Aransas, TX 78373, United States.
J Steroid Biochem Mol Biol. 2017 Mar;167:153-161. doi: 10.1016/j.jsbmb.2016.12.005. Epub 2016 Dec 19.
An essential role for GPER (formerly known as GPR30) in regulating mammalian reproduction has not been identified to date, although it has shown to be involved in the regulation a broad range of other estrogen-dependent functions. In contrast, an important reproductive role for GPER in the maintenance of oocyte meiotic arrest has been identified in teleost fishes, which is briefly reviewed here. Recent studies have clearly shown that ovarian follicle production of estradiol-17β (E) maintains meiotic arrest in several teleost species through activation of GPER coupled to a stimulatory G protein (G) on oocyte plasma membranes resulting in stimulation of cAMP production and maintenance of elevated cAMP levels. Studies with denuded zebrafish oocytes and with microinjection of GPER antisense oligonucleotides into oocytes have demonstrated the requirement for both ovarian follicle production of estrogens and expression of GPER on the oocyte surface for maintenance of meiotic arrest. This inhibitory action of E on the resumption of meiosis is mimicked by the GPER-selective agonist G-1, by the GPER agonists and nuclear ER antagonists, ICI 182,780 and tamoxifen, and also by the xenoestrogen bisphenol-A (BPA) and related alkylphenols. GPER also maintains meiotic arrest of zebrafish oocytes through estrogen- and BPA-dependent GPER activation of epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase (MAPK) signaling. Interestingly, progesterone receptor component 1 (PGRMC1) is also involved in estrogen maintenance of meiotic arrest through regulation of EGFR expression on the oocyte plasma membrane. The preovulatory surge in LH secretion induces the ovarian synthesis of progestin hormones that activate a membrane progestin receptor alpha (mPRα)/inhibitory G protein (Gi) pathway. It also increases ovarian synthesis of the catecholestrogen, 2-hydroxy-estradiol-17β (2-OHE) which inhibits the GPER/Gs/adenylyl cyclase pathway. Both of these LH actions cause declines in oocyte cAMP levels resulting in the resumption of meiosis. GPER is also present on murine oocytes but there are no reports of studies investigating its possible involvement in maintaining meiotic arrest in mammals.
尽管已表明GPER（以前称为GPR30）参与调节广泛的其他雌激素依赖性功能，但迄今为止尚未确定其在调节哺乳动物生殖中的关键作用。相比之下，硬骨鱼中已确定GPER在维持卵母细胞减数分裂停滞中具有重要的生殖作用，在此简要回顾。最近的研究清楚地表明，卵巢卵泡产生的雌二醇-17β（E）通过激活与卵母细胞质膜上的刺激性G蛋白（G）偶联的GPER，维持几种硬骨鱼物种的减数分裂停滞，从而刺激cAMP产生并维持升高的cAMP水平。对裸斑马鱼卵母细胞以及向卵母细胞中显微注射GPER反义寡核苷酸的研究表明，维持减数分裂停滞既需要卵巢卵泡产生雌激素，也需要卵母细胞表面表达GPER。E对减数分裂恢复的这种抑制作用可被GPER选择性激动剂G-1、GPER激动剂和核雌激素受体拮抗剂ICI 182,780和他莫昔芬模拟，也可被异雌激素双酚A（BPA）和相关烷基酚模拟。GPER还通过表皮生长因子受体（EGFR）和丝裂原活化蛋白激酶（MAPK）信号的雌激素和BPA依赖性GPER激活，维持斑马鱼卵母细胞的减数分裂停滞。有趣的是，孕激素受体成分1（PGRMC1）也通过调节卵母细胞质膜上的EGFR表达，参与雌激素维持减数分裂停滞。促黄体生成素（LH）分泌的排卵前激增诱导卵巢合成孕激素激素，激活膜孕激素受体α（mPRα）/抑制性G蛋白（Gi）途径。它还增加卵巢儿茶酚雌激素2-羟基雌二醇-17β（2-OHE）的合成，后者抑制GPER/Gs/腺苷酸环化酶途径。LH的这两种作用都会导致卵母细胞cAMP水平下降，从而导致减数分裂恢复。GPER也存在于小鼠卵母细胞上，但尚无研究报道其可能参与维持哺乳动物的减数分裂停滞。
