PMID- 25348585 OWN - NLM STAT- MEDLINE DCOM- 20150709 LR - 20181202 IS - 1098-2795 (Electronic) IS - 1040-452X (Linking) VI - 81 IP - 11 DP - 2014 Nov TI - Epidermal growth factor-network signaling mediates luteinizing hormone regulation of BNP and CNP and their receptor NPR2 during porcine oocyte meiotic resumption. PG - 1030-41 LID - 10.1002/mrd.22424 [doi] AB - The epidermal growth factor (EGF) network, induced by luteinizing hormone (LH), plays an essential role during the regulation of oocyte maturation, cumulus expansion, and ovulation. Binding of brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) to natriuretic receptor 2 (NPR2) generates cyclic guanosine monophosphate (cGMP), a key inhibitor that sustains porcine oocyte meiotic arrest. This correlation suggests that LH interacts with natriuretic-peptide signaling, possibly via the EGF network, to promote porcine meiotic resumption. In testing this hypothesis, we found that the majority of porcine oocytes remain arrested in the germinal-vesicle stage after 44 hr of co-culturing cumulus-oocyte complexes with 10(7) granulosa cells, which secreted active BNP and CNP; these natriuretic peptides associate with NPR2 on cumulus cells, thereby inhibiting porcine oocyte maturation. This inhibitory effect of BNP and CNP was relieved by EGF-like growth factors, whose expression naturally increases in granulosa cells 18 hr after human chorionic gonadotropin injection. LH and the EGF-like peptide amphiregulin (AREG) decreased BNP and CNP production in granulosa cells and down-regulated NPR2 expression in cumulus cells, which together decreased oocyte cGMP to levels that permit meiotic resumption. The effects of AREG on the gene expression of natriuretic-peptide signaling components and on oocyte maturation were completely blocked by the EGF receptor kinase inhibitor AG1478; the effect of LH, however, was only partially reversed by AG1478. Based on these results, LH regulates natriuretic-peptide signaling, although other pathways also cooperate with the EGF network to induce porcine oocyte maturation. CI - (c) 2014 Wiley Periodicals, Inc. FAU - Zhang, Wenqiang AU - Zhang W AD - State Key Laboratory of Agro-Biotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, People's Republic of China. FAU - Chen, Qian AU - Chen Q FAU - Yang, Ye AU - Yang Y FAU - Liu, Wei AU - Liu W FAU - Zhang, Meijia AU - Zhang M FAU - Xia, Guoliang AU - Xia G FAU - Wang, Chao AU - Wang C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141027 PL - United States TA - Mol Reprod Dev JT - Molecular reproduction and development JID - 8903333 RN - 0 (Amphiregulin) RN - 0 (DNA Primers) RN - 0 (Quinazolines) RN - 0 (Tyrphostins) RN - 114471-18-0 (Natriuretic Peptide, Brain) RN - 127869-51-6 (Natriuretic Peptide, C-Type) RN - 170449-18-0 (RTKI cpd) RN - 9002-67-9 (Luteinizing Hormone) RN - EC 4.6.1.2 (Receptors, Atrial Natriuretic Factor) RN - H2D2X058MU (Cyclic GMP) SB - IM MH - Amphiregulin/*metabolism MH - Animals MH - Cyclic GMP/biosynthesis MH - DNA Primers/genetics MH - Female MH - Granulosa Cells/metabolism MH - In Situ Hybridization MH - Luteinizing Hormone/*metabolism MH - Meiosis/*physiology MH - Natriuretic Peptide, Brain/*metabolism MH - Natriuretic Peptide, C-Type/*metabolism MH - Oocytes/*physiology MH - Quinazolines/pharmacology MH - Radioimmunoassay MH - Real-Time Polymerase Chain Reaction MH - Receptors, Atrial Natriuretic Factor/*metabolism MH - Signal Transduction/*physiology MH - Swine MH - Tyrphostins/pharmacology EDAT- 2014/10/29 06:00 MHDA- 2015/07/15 06:00 CRDT- 2014/10/29 06:00 PHST- 2014/06/17 00:00 [received] PHST- 2014/09/07 00:00 [accepted] PHST- 2014/10/29 06:00 [entrez] PHST- 2014/10/29 06:00 [pubmed] PHST- 2015/07/15 06:00 [medline] AID - 10.1002/mrd.22424 [doi] PST - ppublish SO - Mol Reprod Dev. 2014 Nov;81(11):1030-41. doi: 10.1002/mrd.22424. Epub 2014 Oct 27.