Non-steroid cytosolic hormone receptor ligands

The aryl hydrocarbon receptor (ARH-R or dioxin receptor) is activated by xenobiotics such as 2,3,7,8-tetrachlorodibenzo-j6-dioxin with resultant adverse effects. The activated receptor binds to a xenobiotic-responsive element with the consequent activation of the transcription of particular genes. Cell cycle progression is inhibited by naturally occurring and synthetic flavonoids at concentrations at which they act as agonists of the ARH-R. 

Retinoids (e.g. retinoic acid) are involved in development and in metabolic regulation (e.g. through induction of expression of PEPCK, the rate limiting enzyme in gluconeogenesis). Retinoic acid derives from retinol, which in turn derives from ingestion of plant a-, 3- and /-carotenes and other carotenes. Retinoic acid acts via retinoic acid receptors and retinoid X receptors note that these receptors can heterodimerize in the nucleus with other related hormone receptors such as PPA-Rs. The developmental importance of retinoic acid is underscored by the teratogenicity of retinoic acid and other vitamin A related compounds, notably some compounds developed for anti-acne properties. 

Vitamin D j (cholecalciferol) derives from the photochemical cleavage of 7-dehydrocholes-terol and subsequent successive hydroxylations yield the active vitamin D receptor agonist 

25-dihydroxyvitamin D j (1,25-dihydroxycholecalciferol). Activation of the receptor leads to expression of particular proteins, notably an intestinal Ca2+ binding protein, and regulation of intestinal Ca2+ uptake and Ca2+ sequestration in kidney and bone. Vitamin D2 (ergocalciferol) is industrially obtained from irradiation of yeast-derived ergosterol and is hydroxylated to form an active vitamin D receptor agonist. Vitamin D deficiency causes rickets. 

Finally, there are some so-called orphan cytosolic receptor family receptors for which the physiological agonists are uncertain. However, as detailed in Table 11.2 some plant-derived substances can bind to these receptors. 

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