PMID- 27349986
OWN - NLM
STAT- MEDLINE
DCOM- 20170512
LR  - 20170512
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 123
DP  - 2017 Jan 1
TI  - From dioxin toxicity to putative physiologic functions of the human Ah receptor 
      in homeostasis of stem/progenitor cells.
PG  - 1-7
LID - S0006-2952(16)30141-1 [pii]
LID - 10.1016/j.bcp.2016.06.015 [doi]
AB  - Despite decades of intensive research physiologic Ah receptor (AHR) functions are 
      not yet elucidated. Challenges include marked species differences and dependence 
      of AHR function on the cell type and cellular context. Hints to physiologic 
      functions may be derived (i) from feedback loops between endogenous ligands and 
      substrates of major target enzymes such as CYP1A1 and UGT1A1, and (ii) from 
      dioxin toxicity in human individuals. For example, dioxin-mediated chloracne is 
      probably due to dysregulated homeostasis of sebocyte stem/progenitor cells. 
      Dioxin-mediated inflammatory responses may be due to complex dysregulation of 
      hematopoiesis. Comparison of AHR functions with those of PXR and its target 
      enzyme CYP3A4 may be helpful to emphasize AHR functions in specialized cells: PXR 
      is known to be mainly involved in regulation of systemic metabolism of endo- and 
      xenobiotics. However, AHR may be mostly controlling local homeostasis of signals 
      in specialized cells such as stem/progenitor cells. Accumulating evidence 
      suggests that knowledge about physiologic AHR functions may stimulate drug 
      development.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Bock, Karl Walter
AU  - Bock KW
AD  - Department of Toxicology, Institute of Experimental and Clinical Pharmacology and 
      Toxicology, Wilhelmstrasse 56, D-72074 Tubingen, Germany. Electronic address: 
      bock@uni-tuebingen.de.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20160625
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Dioxins)
RN  - 0 (Ligands)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - EC 2.4.1.- (UGT1A1 enzyme)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
SB  - IM
MH  - Cell Cycle/physiology
MH  - Cell Differentiation/physiology
MH  - Cytochrome P-450 CYP1A1/metabolism
MH  - Dioxins/*toxicity
MH  - Glucuronosyltransferase/metabolism
MH  - *Homeostasis
MH  - Humans
MH  - Ligands
MH  - Receptors, Aryl Hydrocarbon/metabolism/*physiology
MH  - Stem Cells/*cytology
OTO - NOTNLM
OT  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin=TCDD (PubChem CID 15625
OT  - 3,3'-Diindolylmethane, DIM (PubChem CID 3071)
OT  - 6-Formylindolo[3,2-b]carbazole=FICZ (PubChem CID 1863)
OT  - Ah receptor
OT  - Chloracne
OT  - Feedback loops
OT  - PXR
OT  - Stem/progenitor cells
OT  - StemRegenin 1 (PubChem CID 46199207)
OT  - Tranilast (PubChem CID 5282230)
OT  - VAF347 (PubChem CID 10172275)
EDAT- 2016/06/29 06:00
MHDA- 2017/05/13 06:00
CRDT- 2016/06/29 06:00
PHST- 2016/05/12 00:00 [received]
PHST- 2016/06/23 00:00 [accepted]
PHST- 2016/06/29 06:00 [pubmed]
PHST- 2017/05/13 06:00 [medline]
PHST- 2016/06/29 06:00 [entrez]
AID - S0006-2952(16)30141-1 [pii]
AID - 10.1016/j.bcp.2016.06.015 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2017 Jan 1;123:1-7. doi: 10.1016/j.bcp.2016.06.015. Epub 2016 
      Jun 25.