“…In mammals, ATRA functions as a hormone agonist for the retinoic acid receptor family of nuclear transcription factors and directly activates several hundred genes, which contain retinoic acid response elements (RAREs) 2 in their promoters (6,7); it is this global effect on the regulation of gene transcription that renders vitamin A essential for embryonic development, growth, and differentiation in mammals, including humans. -Carotene is cleaved eccentrically at double bonds other than the central one to yield -apocarotenals and -apocarotenones (8 -10), molecules that have been detected in foods (11) and in the blood of both humans (12) and animals (13), but whose function in these is unknown. Here, we show that some of these compounds (particularly -apo-14Ј-carotenal, -apo-14Ј-carotenoic acid, and -apo-13-carotenone) function as antagonists of retinoic acid receptors ␣, , and ␥ and block the ATRA-induced activation of endogenous genes that contain RAREs in their promoters.…”