PMID- 27268078
OWN - NLM
STAT- MEDLINE
DCOM- 20171227
LR  - 20181113
IS  - 1944-9917 (Electronic)
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 30
IP  - 8
DP  - 2016 Aug
TI  - Phoenixin Activates Immortalized GnRH and Kisspeptin Neurons Through the Novel 
      Receptor GPR173.
PG  - 872-88
LID - 10.1210/me.2016-1039 [doi]
AB  - Reproductive function is coordinated by kisspeptin (Kiss) and GnRH neurons. 
      Phoenixin-20 amide (PNX) is a recently described peptide found to increase 
      GnRH-stimulated LH secretion in the pituitary. However, the effects of PNX in the 
      hypothalamus, the putative signaling pathways, and PNX receptor have yet to be 
      identified. The mHypoA-GnRH/GFP and mHypoA-Kiss/GFP-3 cell lines represent 
      populations of GnRH and Kiss neurons, respectively. PNX increased GnRH and GnRH 
      receptor (GnRH-R) mRNA expression, as well as GnRH secretion, in the 
      mHypoA-GnRH/GFP cell model. In the mHypoA-Kiss/GFP-3 cell line, PNX increased 
      Kiss1 mRNA expression. CCAAT/enhancer-binding protein (C/EBP)-beta, octamer 
      transcription factor-1 (Oct-1), and cAMP response element binding protein (CREB) 
      binding sites are localized to the 5' flanking regions of the GnRH, GnRH-R, and 
      Kiss1 genes. PNX decreased C/EBP-beta mRNA expression in both cell models and 
      increased Oct-1 mRNA expression in the mHypoA-GnRH/GFP neurons. PNX increased 
      CREB phosphorylation in both cell models and phospho-ERK1/2 in the 
      mHypoA-GnRH/GFP cell model, whereas inhibiting the cAMP/protein kinase A pathway 
      prevented PNX induction of GnRH and Kiss1 mRNA expression. Importantly, we 
      determined that the G protein-coupled receptor, GPR173, was strongly expressed in 
      both GnRH and kisspeptin cell models and small interfering RNA knockdown of 
      GPR173 prevented the PNX-mediated up-regulation of GnRH, GnRH-R, and Kiss1 mRNA 
      expression and the down-regulation of C/EBP-beta mRNA expression. PNX also increased 
      GPR173 mRNA expression in the mHypoA-GnRH/GFP cells. Taken together, these 
      studies are the first to implicate that PNX acts through GPR173 to activate the 
      cAMP/protein kinase A pathway through CREB, and potentially C/EBP-beta and/or Oct-1 
      to increase GnRH, GnRH-R, and Kiss1 gene expression, ultimately having a 
      stimulatory effect on reproductive function.
FAU - Treen, Alice K
AU  - Treen AK
AD  - Departments of Physiology (A.K.T., V.L., D.D.B.), Medicine (D.D.B.), and 
      Obstetrics and Gynaecology (D.D.B.), University of Toronto, and Division of 
      Cellular and Molecular Biology (D.D.B.), Toronto General Hospital Research 
      Institute, University Health Network, Toronto, Ontario, Canada M5S 1A8.
FAU - Luo, Vicky
AU  - Luo V
AD  - Departments of Physiology (A.K.T., V.L., D.D.B.), Medicine (D.D.B.), and 
      Obstetrics and Gynaecology (D.D.B.), University of Toronto, and Division of 
      Cellular and Molecular Biology (D.D.B.), Toronto General Hospital Research 
      Institute, University Health Network, Toronto, Ontario, Canada M5S 1A8.
FAU - Belsham, Denise D
AU  - Belsham DD
AD  - Departments of Physiology (A.K.T., V.L., D.D.B.), Medicine (D.D.B.), and 
      Obstetrics and Gynaecology (D.D.B.), University of Toronto, and Division of 
      Cellular and Molecular Biology (D.D.B.), Toronto General Hospital Research 
      Institute, University Health Network, Toronto, Ontario, Canada M5S 1A8.
LA  - eng
PT  - Journal Article
DEP - 20160606
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Amides)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (GPR173 protein, mouse)
RN  - 0 (Kiss1 protein, mouse)
RN  - 0 (Kisspeptins)
RN  - 0 (Peptides)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Receptors, LHRH)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
SB  - IM
MH  - Amides/chemistry/*pharmacology
MH  - Animals
MH  - Cell Line
MH  - Cells, Cultured
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Gonadotropin-Releasing Hormone/*metabolism
MH  - Hypothalamus/drug effects/metabolism
MH  - Kisspeptins/genetics/*metabolism
MH  - Mice
MH  - Neurons/drug effects/*metabolism
MH  - Peptides/chemistry/*pharmacology
MH  - Phosphorylation/drug effects
MH  - Receptors, G-Protein-Coupled/genetics/*metabolism
MH  - Receptors, LHRH/metabolism
PMC - PMC5414621
EDAT- 2016/06/09 06:00
MHDA- 2017/12/28 06:00
PMCR- 2017/08/01
CRDT- 2016/06/09 06:00
PHST- 2016/06/09 06:00 [entrez]
PHST- 2016/06/09 06:00 [pubmed]
PHST- 2017/12/28 06:00 [medline]
PHST- 2017/08/01 00:00 [pmc-release]
AID - ME-16-1039 [pii]
AID - 10.1210/me.2016-1039 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2016 Aug;30(8):872-88. doi: 10.1210/me.2016-1039. Epub 2016 Jun 
      6.