Hormonal Coordination of Natriuretic Peptide Type C and Natriuretic Peptide Receptor 3 Expression in Mouse Granulosa Cells
Hormonal Coordination of Natriuretic Peptide Type C and Natriuretic Peptide Receptor 3 Expression in Mouse Granulosa Cells
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DOI：
10.1095/biolreprod.112.104810
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发表时间：
2013-02-01
影响因子：
3.6
通讯作者：
Eppig, John J.
中科院分区：
文献类型：
--
作者：
Lee, Kyung-Bon;Zhang, Meijia;Eppig, John J.
C型利钠肽（NPPC）及其受体利钠肽受体2（NPR 2）调节卵泡中的cGMP，并参与维持卵母细胞减数分裂阻滞。我们在体内和体外研究了小鼠颗粒细胞中Nppc表达的调节。在体内的壁颗粒细胞（MGCs）中，eCG引起Nppc mRNA的增加，随后的人绒毛膜促性腺激素（hCG）治疗引起Nppc mRNA的减少。建立了一个培养系统，用于从未用马绒毛膜促性腺激素刺激的卵泡中分离的MGCs，以进一步确定控制Nppc表达的机制。在这个系统中，Nppc mRNA的表达增加雌二醇（E2），与增强卵泡刺激素（FSH），但FSH或黄体生成素（LH）单独没有影响。因此，雌激素对调节Nppc表达很重要，可能是通过反馈机制增强促性腺激素的作用。在体外用E2加FSH处理的MGCs中，随后用EGF处理，而不是LH，降低Nppc mRNA。MGCs表达更高水平的Nppc和Lhcgr mRNA比卵丘细胞。卵母细胞衍生的旁分泌因子抑制卵丘细胞Lhcgr表达，但不抑制Nppc表达。因此，较高的Nppc表达的MGCs是不是卵丘细胞中的表达的卵母细胞抑制的结果。LH诱导的NPPC减少的另一种可能的调节剂是NPR3，一种NPPC清除受体。人绒毛膜促性腺激素增加Npr3在体内的表达和LH增加Npr3 mRNA在培养的MGCs，独立的EGF受体激活。有趣的是，尽管Npr3 mRNA增加，但hCG诱导的卵巢NPPC减少通常发生在Npr3突变体（lgj）中，因此NPR3可能不参与卵巢NPPC水平或卵母细胞发育的调节。
Natriuretic peptide type C (NPPC) and its receptor natriuretic peptide receptor 2 (NPR2) regulate cGMP in ovarian follicles and participate in maintaining oocyte meiotic arrest. We investigated the regulation of Nppc expression in mouse granulosa cells in vivo and in vitro. In mural granulosa cells (MGCs) in vivo, eCG caused an increase in Nppc mRNA, and subsequent human chorionic gonadotropin (hCG) treatment caused a decrease. A culture system was established for MGCs isolated from follicles not stimulated with equine chorionic gonadotropin to further define the mechanisms controlling Nppc expression. In this system, expression of Nppc mRNA was increased by estradiol (E2), with augmentation by follicle-stimulating hormone (FSH), but FSH or luteinizing hormone (LH) alone had no effect. Thus, estrogens are important for regulating Nppc expression, probably by feedback mechanisms enhancing the action of gonadotropins. In MGCs treated with E2 plus FSH in vitro, subsequent treatment with EGF, but not LH, decreased Nppc mRNA. MGCs express higher levels of both Nppc and Lhcgr mRNAs than cumulus cells. Oocyte-derived paracrine factors suppressed cumulus cell Lhcgr but not Nppc expression. Thus, higher Nppc expression by MGCs is not the result of oocyte suppression of expression in cumulus cells. Another possible regulator of the LH-induced NPPC decrease is NPR3, an NPPC clearance receptor. Human chorionic gonadotropin increased Npr3 expression in vivo and LH increased Npr3 mRNA in cultured MGCs, independently of EGF receptor activation. Interestingly, despite the increase in Npr3 mRNA, the hCG-induced decrease in ovarian NPPC occurred normally in an Npr3 mutant (lgj), thus NPR3 probably does not participate in regulation of ovarian NPPC levels or oocyte development.