title: Epidermal growth factor-network signaling mediates luteinizing hormone regulation of BNP and CNP and their receptor NPR2 during porcine oocyte meiotic resumption.
abstract: 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.
authors.affiliation: State Key Laboratory of Agro-Biotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, People's Republic of China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.forename: Ye
authors.initials: Y
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Meijia
authors.initials: M
authors.lastname: Zhang
authors.forename: Guoliang
authors.initials: G
authors.lastname: Xia
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
mesh_terms: D066258:Amphiregulin / Q000378:metabolism*; D000818:Animals; D006152:Cyclic GMP / Q000096:biosynthesis; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006107:Granulosa Cells / Q000378:metabolism; D017403:In Situ Hybridization; D007986:Luteinizing Hormone / Q000378:metabolism*; D008540:Meiosis / Q000502:physiology*; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism*; D009865:Oocytes / Q000502:physiology*; D011799:Quinazolines / Q000494:pharmacology; D011863:Radioimmunoassay; D060888:Real-Time Polymerase Chain Reaction; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013552:Swine; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D066258:Amphiregulin; D017931:DNA Primers; D011799:Quinazolines; D020032:Tyrphostins; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; C101044:RTKI cpd; D007986:Luteinizing Hormone; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP