Retinoid Receptors, Their Ligands, and Teratogenesis: Synergy and Specificity of Effects

Vitamin A and metabolites (retinoids) control numerous processes which are critical for reproduction and development such as differentiation, proliferation, apoptosis and morphogenesis (De Luca et al. 1995). Evidence has accumulated since the discovery of the retinoid receptors a decade ago (Petkovic et al. 1987; Giguere et al. 1987) that these nuclear receptors may be involved in many of these processes. Retinoid receptors are ligand-activated transcription factors which control the expression of a number of target genes involved in development such as growth factors, growth factor receptors, cell adhesion molecules, intercellular matrix molecules, other transcription factors such as hox genes, some hormones and cytokines, as well as other receptors of the hormone receptor superfamily; furthermore, retinoid pathways themselves are influenced via the control of expression of retinoid binding proteins, metabolizing enzymes and autoregulation of retinoid receptors (Kastner et al. 1995; Chambon 1996; Morris-Kay and Sokolova 1996; Van Der Saag 1996; Nagpal and Chandrarathna 1996; Smith et al. 1998).