PMID- 21047912
OWN - NLM
STAT- MEDLINE
DCOM- 20110411
LR  - 20211020
IS  - 1944-9917 (Electronic)
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 25
IP  - 1
DP  - 2011 Jan
TI  - LH-induced neuregulin 1 (NRG1) type III transcripts control granulosa cell 
      differentiation and oocyte maturation.
PG  - 104-16
LID - 10.1210/me.2010-0225 [doi]
AB  - Epidermal growth factor (EGF)-like factors [amphiregulin (AREG), betacellulin, 
      and epiregulin] are induced by LH and activate the EGF receptor (ERBB1)/ERK1/2 
      pathway in granulosa cells and cumulus cells of preovulatory follicles to impact 
      ovulation. However, the expression and roles of other ERBB family members and 
      their ligands have not been explored in detail. Herein, we document that two 
      transcripts of the neuregulin (Nrg1) gene are expressed in granulosa cells, and 
      that the type III Nrg1 is induced during ovulation in an ERK1/2 and 
      C/EBPbeta-dependent manner. Western blotting shows that intact (75 kDa) and secreted 
      (45 kDa) forms of neuregulin 1 (NRG1) are present in the ovary. NRG1 likely binds 
      to ERBB3/ERBB2 complexes that are expressed in granulosa cells and cumulus cells. 
      In cultured granulosa cells, NRG1 selectively stimulates the phosphorylation of 
      AKT/PKB compared to ERK1/2. However, when granulosa cells were cultured with NRG1 
      and AREG, the phosphorylation of ERK1/2 was markedly enhanced as compared with 
      that by AREG alone. Cotreatment with NRG1 and AREG also increased progesterone 
      production. When cumulus-oocyte complexes (COCs) were cultured with both NRG1 and 
      AREG, the matured oocytes exhibited significantly higher developmental competence 
      as compared with that of oocytes cultured with AREG alone. Collectively, these 
      results document that the expression of type III NRG1 is induced in granulosa 
      cells during ovulation and that NRG1 enhances AREG-induced ERK1/2 phosphorylation 
      in both granulosa cells and cumulus cells. The NRG1 pathway has two roles: one is 
      to enhance AREG-induced progesterone production in granulosa cells, and the other 
      is to regulate oocyte maturation by a cumulus cell-dependent mechanism.
FAU - Noma, Noritaka
AU  - Noma N
AD  - Laboratory of Reproductive Endocrinology, Graduate School of Biosphere Science, 
      Hiroshima University, Higashi-Hiroshima, Hiroshima, Japan.
FAU - Kawashima, Ikko
AU  - Kawashima I
FAU - Fan, Heng-Yu
AU  - Fan HY
FAU - Fujita, Youko
AU  - Fujita Y
FAU - Kawai, Tomoko
AU  - Kawai T
FAU - Tomoda, Yoshinori
AU  - Tomoda Y
FAU - Mihara, Toshihiro
AU  - Mihara T
FAU - Richards, Joanne S
AU  - Richards JS
FAU - Shimada, Masayuki
AU  - Shimada M
LA  - eng
GR  - R56 HD016229/HD/NICHD NIH HHS/United States
GR  - T32 HD007495/HD/NICHD NIH HHS/United States
GR  - HD-16229/HD/NICHD NIH HHS/United States
GR  - HD-07495/HD/NICHD NIH HHS/United States
GR  - U54 HD007495/HD/NICHD NIH HHS/United States
GR  - R37 HD016229/HD/NICHD NIH HHS/United States
GR  - R01 HD016229/HD/NICHD NIH HHS/United States
GR  - P30 HD007495/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101103
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Areg protein, mouse)
RN  - 0 (Chorionic Gonadotropin)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Ligands)
RN  - 0 (Neuregulin-1)
RN  - 0 (Nrg1 protein, mouse)
RN  - 0 (RNA, Messenger)
RN  - 9002-67-9 (Luteinizing Hormone)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Amphiregulin
MH  - Animals
MH  - Base Sequence
MH  - Cell Differentiation/*drug effects
MH  - Cells, Cultured
MH  - Chorionic Gonadotropin/pharmacology
MH  - Cumulus Cells/cytology/drug effects/enzymology
MH  - EGF Family of Proteins
MH  - Embryonic Development/drug effects
MH  - Enzyme Activation/drug effects
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Glycoproteins/pharmacology
MH  - Granulosa Cells/*cytology/drug effects/enzymology
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/pharmacology
MH  - Ligands
MH  - Luteinizing Hormone/*pharmacology
MH  - Mice
MH  - Molecular Sequence Data
MH  - Neuregulin-1/*genetics/metabolism/pharmacology
MH  - Oocytes/*cytology/drug effects
MH  - Ovulation/drug effects
MH  - Promoter Regions, Genetic/genetics
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptor Protein-Tyrosine Kinases/metabolism
MH  - Time Factors
PMC - PMC3089030
EDAT- 2010/11/05 06:00
MHDA- 2011/04/13 06:00
PMCR- 2012/01/01
CRDT- 2010/11/05 06:00
PHST- 2010/11/05 06:00 [entrez]
PHST- 2010/11/05 06:00 [pubmed]
PHST- 2011/04/13 06:00 [medline]
PHST- 2012/01/01 00:00 [pmc-release]
AID - me.2010-0225 [pii]
AID - 4755 [pii]
AID - 10.1210/me.2010-0225 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2011 Jan;25(1):104-16. doi: 10.1210/me.2010-0225. Epub 2010 Nov 
      3.