The Intersection Between the Aryl Hydrocarbon Receptor (AhR)‐ and Retinoic Acid‐Signaling Pathways

• Published in: Vitamin A Vol. 75; pp. 33 - 67
• Main Authors: Murphy, Kyle A., Quadro, Loredana, White, Lori A.
• Format: Book Chapter Journal Article
• Language: English
• Published: United States Elsevier Science & Technology 2007
• Subjects: Animals; Biochemistry; Endocrinology; Gene Expression Regulation, Enzymologic - physiology; Humans; Metabolism; Receptors, Aryl Hydrocarbon - chemistry; Receptors, Aryl Hydrocarbon - metabolism; Receptors, Aryl Hydrocarbon - physiology; Receptors, Retinoic Acid - chemistry; Receptors, Retinoic Acid - metabolism; Receptors, Retinoic Acid - physiology; Signal Transduction - physiology; Transcription Factors - metabolism; Transcription Factors - physiology; Tretinoin - chemistry; Tretinoin - metabolism; Tretinoin - physiology
• ISBN: 0127098755; 9780127098753
• ISSN: 0083-6729; 2162-2620
• DOI: 10.1016/S0083-6729(06)75002-6

Data from a variety of animal and cell culture model systems have demonstrated an interaction between the aryl hydrocarbon receptor (AhR)‐ and retinoic acid (RA)‐signaling pathways. The AhR11Abbreviations: ADH, alcohol dehydrogenase; AhR, aryl hydrocarbon receptor; ALDH, aldehyde dehydrogenase; Arnt, AhR nuclear translocator; atRA, all‐trans RA; CRABP, cellular retinoic acid‐binding protein; CRBPI, cellular retinol‐binding protein type I; CYP450, cytochrome P450; GST, glutathione S‐transferases; HAT, histone acetyltransferase; HDACs, histone deacetylases; HMTs, histone methyltransferases; LRAT, lecithin:retinol acyltransferase; MMPs, matrix metalloproteinases; RAL, retinal; RALDH, retinaldehyde dehydrogenase; RAR, RAR gene; RAREs, retinoic acid response elements; RARs, retinoic acid receptors; RBP, retinol‐binding protein; RDH, retinol dehydrogenase; RE, retinyl ester; REHs, retinyl ester hydrolases; ROH, retinol; RXR, RXR gene; RXRs, retinoid X receptors; SCADs, short‐chain alcohol dehydrogenases; SMRT, silencing mediator of retinoid and thyroid receptors; TCDD, 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin; UGTs, UDP‐glucuronosyltransferases; XREs, xenobiotic response elements; N‐CoR, nuclear receptors corepressor; RA, retinoic acid. was originally identified as the receptor for the polycyclic aromatic hydrocarbon family of environmental contaminants; however, recent data indicate that the AhR binds to a variety of endogenous and exogenous compounds, including some synthetic retinoids. In addition, activation of the AhR pathway alters the function of nuclear hormone‐signaling pathways, including the estrogen, thyroid, and RA pathways. Activation of the AhR pathway through exposure to environmental compounds results in significant changes in RA synthesis, catabolism, transport, and excretion. Some effects on retinoid homeostasis mediated by the AhR pathway may result from the interactions of these two pathways at the level of activating or repressing the expression of specific genes. This chapter will review these two pathways, the evidence demonstrating a link between them, and the data indicating the molecular basis of the interactions between these two pathways.