ABSTRACT
The elucidation of the physiological roles played by vitamins has always been a
major concern of nutritionists and biochemists. In humans, vitamin A deficiency
(VAD) leads to night blindness in milder forms, whereas more severe progression
can lead to corneal malformations, e.g., xerophthalmia. Besides visual defects,
this deficiency affects the immune system, leads to infertility, and causes
malformations during embryogenesis. The molecular basis for these diverse
effects is found in the dual role exerted by vitamin A derivatives in animal
physiology: In all visual systems, retinal or closely related compounds such as
3-hydroxyretinal serve as the chromophores of the visual pigments (rhodopsin)
(1,2). In vertebrates, the vitamin A derivative retinoic acid (RA) is a major signal
controlling a wide range of biological processes. RA is the ligand of two classes
of nuclear receptors, the retinoic acid receptors (RARs) and the retinoid X
receptors (RXRs) (3, 4; reviewed in 5 and 6). The active receptor complex,
involved in processes as diverse as pattern formation during embryonic
development, cell differentiation, and control of metabolic activity, is an RAR/ RXR heterodimer that binds DNA regulatory sequences and regulates gene
transcription in response to ligand binding. RXR is not only the heterodimer
partner of the RAR receptor but also an obligate partner for other nuclear
receptors (orphan receptors) controlling a wide range of activities in lipid
metabolism (for recent review, see Ref. 7).
