PMID- 21237132 OWN - NLM STAT- MEDLINE DCOM- 20110406 LR - 20181201 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 405 IP - 2 DP - 2011 Feb 11 TI - Epiregulin-dependent amphiregulin expression and ERBB2 signaling are involved in luteinizing hormone-induced paracrine signaling pathways in mouse ovary. PG - 319-24 LID - 10.1016/j.bbrc.2011.01.039 [doi] AB - Sustained EGF receptor (EGFR) phosphorylation by de novo synthesis of EGFR ligands plays an essential role in mediating luteinizing hormone (LH)-induced ovulation process in the preovulatory follicles (POFs). In the present study, the effect of epiregulin (EREG) on oocyte maturation and ovulation was investigated using Ereg knockout (Ereg-/-) mice congenic on a C57BL/6 background. Rate of spontaneous oocyte meiotic resumption of denuded oocytes (DOs) or cumulus cell-oocyte complexes (COCs) in vitro is similar between wild-type and Ereg-/- mice. However, gonadotropin-induced meiotic resumption in vivo is attenuated, and the number of COCs with expanded cumulus matrix and superovulated eggs dramatically decrease in Ereg-/- mice. Nonetheless, the number of eggs ovulated during normal estrus cycles and litter sizes in Ereg-/- mice are comparable to those of wild-type littermates. In contrast to other EGFR ligands, induction of amphiregulin (Areg) mRNA is severely reduced in ovaries collected from Ereg-/- mice either after human chorionic gonadotropin (hCG) treatment in immature mice or LH surge in adults. Gonadotropin-induced EGFR and ERBB2 phosphorylation in ovaries is attenuated in immature Ereg-/- mice, and MAPK3/1 phosphorylation and prostaglandin synthase 2 (PTGS2) protein levels are reduced. This attenuation, however, is no longer detectable in adult Ereg-/- mice after LH surge. This study implicates that EREG mediates signals downstream of Areg mRNA expression and that EGFR-ERBB2 signals contributes to regulation of ovulation process. CI - Copyright (c) 2011 Elsevier Inc. All rights reserved. FAU - Kim, Kyoungmi AU - Kim K AD - Department of Life Science and Pharmaceutical Science, Ewha Womans University, Seoul, South Korea. FAU - Lee, Hyunji AU - Lee H FAU - Threadgill, David W AU - Threadgill DW FAU - Lee, Daekee AU - Lee D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110113 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (AREG protein, human) RN - 0 (Amphiregulin) RN - 0 (Areg protein, mouse) RN - 0 (EGF Family of Proteins) RN - 0 (EREG protein, human) RN - 0 (Epiregulin) RN - 0 (Ereg protein, mouse) RN - 0 (Glycoproteins) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (RNA, Messenger) RN - 62229-50-9 (Epidermal Growth Factor) RN - 9002-67-9 (Luteinizing Hormone) RN - EC 2.7.10.1 (EGFR protein, mouse) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.10.1 (Erbb2 protein, mouse) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Amphiregulin MH - Animals MH - EGF Family of Proteins MH - Epidermal Growth Factor/genetics/*metabolism MH - Epiregulin MH - ErbB Receptors/metabolism MH - Female MH - Glycoproteins/*biosynthesis/genetics MH - Intercellular Signaling Peptides and Proteins/*biosynthesis/genetics MH - Luteinizing Hormone/*metabolism MH - Meiosis MH - Mice MH - Mice, Inbred C57BL MH - Mice, Mutant Strains MH - Ovary/cytology/metabolism/*physiology MH - *Ovulation MH - Phosphorylation MH - RNA, Messenger/biosynthesis MH - Receptor, ErbB-2/*metabolism MH - Signal Transduction EDAT- 2011/01/18 06:00 MHDA- 2011/04/07 06:00 CRDT- 2011/01/18 06:00 PHST- 2011/01/05 00:00 [received] PHST- 2011/01/08 00:00 [accepted] PHST- 2011/01/18 06:00 [entrez] PHST- 2011/01/18 06:00 [pubmed] PHST- 2011/04/07 06:00 [medline] AID - S0006-291X(11)00058-1 [pii] AID - 10.1016/j.bbrc.2011.01.039 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2011 Feb 11;405(2):319-24. doi: 10.1016/j.bbrc.2011.01.039. Epub 2011 Jan 13.