The Retinoid Signaling System — A Target in Dioxin Toxicity

Abstract

This review summarizes the available data on the effects of dioxins on retinoid levels, retinoid-related enzyme activities, and toxicological endpoints that have been correlated to retinoid effects. Similarities between dioxin toxicity and retinoid deficiency as well as retinoid excess are pointed out. Several possible levels of interaction between the dioxin and the retinoid signaling pathways are discussed, including the involvement of the Ah receptor, altered retinoic acid homeostasis, and an altered set point for retinoid storage. A hypothesis for the effect of dioxins on retinoids is suggested. In this hypothesis, comprising two cascades of effects on the molecular level, the effect of dioxins on retinoic acid levels is central.

Exocrine pancreatic pathology in female Harlan Sprague-Dawley rats after chronic treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin-like compounds.

“…TCDD influences and disturbs vitamin A dynamics and metabolism; vitamin A metabolites are known to affect the endocrine and exocrine glandular cell integrity (Fattore et al 2000;Nilsson and Hakansson 2002;Schmidt et al 2003). Certain synthetic retinoids, administered in the diet for 1 year at a dose of 0.5-2 mmol/kg, have chemopreventive potential, reducing the progression of pancreatic carcinomas induced in rats by five weekly injections of azaserine (Longnecker et al 1983).…”

Role of Fat-Soluble Vitamins A and D in the Pathogenesis of Influenza: A New Perspective

“…e RARs and RXRs exist as three distinct gene products-, , and . Upon ligand activation, these receptors function as heterodimeric transcription factors and control the expression of target genes by binding to speci�c DNA sequences, termed RA response elements (RAREs) [70,71].…”

Estrogen Inhibits Development of Yolk Veins and Causes Blood Clotting in Transgenic Medaka Fish Overexpressing Estrogen Receptor

“…Finally we examined for the well-known role of AHR in RA metabolism (Nilsson and Hakansson, 2002). If activation of AHR by agonist ( β -NF) reduced in vivo RA level, the combination of β-NF and DEAB would further reduce it, then increase the rate of vascular abnormalities.…”

“…In experimental animals exposed to dioxin, a highly toxic environmental pollutant which binds to and activates AHR, decreased hepatic retinoid levels are a well-characterized effect (Nilsson and Hakansson, 2002). Mice lacking a functional AHR have greatly increased liver levels of retinoic acid (Andreola et al ., 1997).…”