PMID- 16543407
OWN - NLM
STAT- MEDLINE
DCOM- 20060727
LR  - 20141120
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 20
IP  - 6
DP  - 2006 Jun
TI  - Paracrine and autocrine regulation of epidermal growth factor-like factors in 
      cumulus oocyte complexes and granulosa cells: key roles for prostaglandin 
      synthase 2 and progesterone receptor.
PG  - 1352-65
AB  - The molecular bridges that link the LH surge with functional changes in cumulus 
      cells that possess few LH receptors are being unraveled. Herein we document that 
      epidermal growth factor (EGF)-like factors amphiregulin (Areg), epiregulin 
      (Ereg), and betacellulin (Btc) are induced in cumulus oocyte complexes (COCs) by 
      autocrine and paracrine mechanisms that involve the actions of prostaglandins 
      (PGs) and progesterone receptor (PGR). Areg and Ereg mRNA and protein levels were 
      reduced significantly in COCs and ovaries collected from prostaglandin synthase 2 
      (Ptgs2) null mice and Pgr null (PRKO) mice at 4 h and 8 h after human chorionic 
      gonadotropin, respectively. In cultured COCs, FSH/forskolin induced Areg mRNA 
      within 0.5 h that peaked at 4 h, a process blocked by inhibitors of p38MAPK 
      (SB203580), MAPK kinase (MEK) 1 (PD98059), and PTGS2 (NS398) but not protein 
      kinase A (PKA) (KT5720). Conversely, AREG but not FSH induced Ptsg2 mRNA at 0.5 h 
      with peak expression of Ptgs2 and Areg mRNAs at 4 h, processes blocked by the EGF 
      receptor tyrosine kinase inhibitor AG1478 (AG), PD98059, and NS398. PGE2 reversed 
      the inhibitory effects of AG on AREG-induced expression of Areg but not Ptgs2, 
      placing Ptgs2 downstream of EGF-R signaling. Phorbol 12-myristate 13-acetate 
      (PMA) and adenovirally expressed PGRA synergistically induced Areg mRNA in 
      granulosa cells. In COCs, AREG not only induced genes that impact matrix 
      formation but also genes involved in steroidogenesis (StAR, Cyp11a1) and immune 
      cell-like functions (Pdcd1, Runx1, Cd52). Collectively, FSH-mediated induction of 
      Areg mRNA via p38MAPK precedes AREG induction of Ptgs2 mRNA via ERK1/2. PGs 
      acting via PTGER2 in cumulus cells provide a secondary, autocrine pathway to 
      regulate expression of Areg in COCs showing critical functional links between G 
      protein-coupled receptor and growth factor receptor pathways in ovulating 
      follicles.
FAU - Shimada, Masayuki
AU  - Shimada M
AD  - Department of Molecular Cellular Biology, Baylor College of Medicine, One Baylor 
      Plaza, Houston, Texas 77030, USA.
FAU - Hernandez-Gonzalez, Inmaculada
AU  - Hernandez-Gonzalez I
FAU - Gonzalez-Robayna, Ignacio
AU  - Gonzalez-Robayna I
FAU - Richards, JoAnne S
AU  - Richards JS
LA  - eng
GR  - HD-07495/HD/NICHD NIH HHS/United States
GR  - HD-16229/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 - 20060316
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 (BTC protein, human)
RN  - 0 (Betacellulin)
RN  - 0 (Btc protein, mouse)
RN  - 0 (DNA Primers)
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  - 0 (Receptors, Progesterone)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Amphiregulin
MH  - Animals
MH  - Autocrine Communication
MH  - Base Sequence
MH  - Betacellulin
MH  - Cyclooxygenase 2/deficiency/genetics/*metabolism
MH  - DNA Primers/genetics
MH  - EGF Family of Proteins
MH  - Epidermal Growth Factor/genetics/*metabolism
MH  - Epiregulin
MH  - Female
MH  - Glycoproteins/genetics
MH  - Granulosa Cells/*metabolism
MH  - Intercellular Signaling Peptides and Proteins/genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Models, Biological
MH  - Oocytes/*metabolism
MH  - Paracrine Communication
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Receptors, Progesterone/deficiency/genetics/*metabolism
EDAT- 2006/03/18 09:00
MHDA- 2006/07/28 09:00
CRDT- 2006/03/18 09:00
PHST- 2006/03/18 09:00 [pubmed]
PHST- 2006/07/28 09:00 [medline]
PHST- 2006/03/18 09:00 [entrez]
AID - me.2005-0504 [pii]
AID - 10.1210/me.2005-0504 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2006 Jun;20(6):1352-65. doi: 10.1210/me.2005-0504. Epub 2006 Mar 
      16.