PMID- 23136296
OWN - NLM
STAT- MEDLINE
DCOM- 20130605
LR  - 20211021
IS  - 1529-7268 (Electronic)
IS  - 0006-3363 (Print)
IS  - 0006-3363 (Linking)
VI  - 88
IP  - 1
DP  - 2013 Jan
TI  - EGF-like ligands mediate progesterone's anti-apoptotic action on macaque 
      granulosa cells.
PG  - 18
LID - 10.1095/biolreprod.112.103002 [doi]
LID - 18
AB  - A local autocrine/paracrine role for progesterone is an absolute requirement for 
      corpus luteum formation in primates. Despite this, the mechanism(s) remain 
      obscure, although existing data suggest an anti-apoptotic action to be central. 
      There are a limited number of progestin-regulated gene targets identified in the 
      luteinizing primate follicle, suggesting that a small number of important genes 
      may mediate progesterone action. Possible gene targets could be the epidermal 
      growth factor (EGF) family members amphiregulin (AREG) and epiregulin (EREG). 
      Using macaques undergoing controlled ovarian stimulation cycles, we show that the 
      phosphorylation of EGF receptor (EGFR), ERK 1/2, and AKT increases 6 h after an 
      ovulatory human chorionic gonadotropin (hCG) stimulus and remains activate 
      through 24 h. Immunoreactive EREG and AREG ligands in the follicular fluid both 
      increased in a time frame commensurate with EGFR phosphorylation. The mRNA 
      expression of AREG and EREG in nonluteinized granulosa cells (NLGC) was induced 
      in culture with hCG, an effect blocked by progesterone receptor (PGR) 
      antagonists. Overexpression of PGR B in NLGC and treatment with a 
      nonmetabolizable progestin did not increase either gene, indicating both 
      progesterone and luteinizing hormone/CG are necessary. Addition of EGF and 
      EGF-like ligands did not promote steroidogenesis in vitro by granulosa cells in 
      the presence of gonadotropin, but were able to partially reverse RU486-induced 
      cell death. These data suggest that progesterone promotes the expression of AREG 
      and EREG, which in turn maintain viability of luteinizing granulosa cells, 
      representing one possible mechanism whereby progesterone promotes corpus luteum 
      formation in the primate.
FAU - Puttabyatappa, Muraly
AU  - Puttabyatappa M
AD  - Department of Obstetrics and Gynecology, University of Kentucky College of 
      Medicine, MS331 UKMC, 800 Rose St., Lexington, KY 40536-0298, USA. 
      mpbyatappa@uky.edu
FAU - Brogan, Rebecca S
AU  - Brogan RS
FAU - Vandevoort, Catherine A
AU  - Vandevoort CA
FAU - Chaffin, Charles L
AU  - Chaffin CL
LA  - eng
GR  - RR00169/RR/NCRR NIH HHS/United States
GR  - P51 RR000169/RR/NCRR NIH HHS/United States
GR  - HD043358/HD/NICHD NIH HHS/United States
GR  - R01 HD043358/HD/NICHD NIH HHS/United States
GR  - RR13439/RR/NCRR NIH HHS/United States
GR  - R01 RR013439/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130125
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - 0 (Chorionic Gonadotropin)
RN  - 0 (RNA, Messenger)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 62229-50-9 (Epidermal Growth Factor)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Chorionic Gonadotropin/pharmacology
MH  - Epidermal Growth Factor/*physiology
MH  - Female
MH  - Follicular Fluid
MH  - Gene Expression Regulation/physiology
MH  - Granulosa Cells/*drug effects/physiology
MH  - *Macaca
MH  - Phosphorylation
MH  - Progesterone/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Transcriptome
PMC - PMC4434938
EDAT- 2012/11/09 06:00
MHDA- 2013/06/06 06:00
PMCR- 2014/01/01
CRDT- 2012/11/09 06:00
PHST- 2012/11/09 06:00 [entrez]
PHST- 2012/11/09 06:00 [pubmed]
PHST- 2013/06/06 06:00 [medline]
PHST- 2014/01/01 00:00 [pmc-release]
AID - biolreprod.112.103002 [pii]
AID - 10.1095/biolreprod.112.103002 [doi]
PST - epublish
SO  - Biol Reprod. 2013 Jan 25;88(1):18. doi: 10.1095/biolreprod.112.103002. Print 2013 
      Jan.