THE ORPHAN RECEPTOR FAMILY RZR ROR, MELATONIN AND 5-LIPOXYGENASE - ANUNEXPECTED RELATIONSHIP/

The orphan receptors RZR alpha, RZR beta, ROR alpha 1, RZR alpha 2, RO R alpha 3, and ROR gamma form a subfamily within the superfamily of nu clear hormone receptors. Recently, experimental evidence that the pine al gland hormone melatonin is the natural ligand for these nuclear rec eptors has come to light. This discovery is rather surprising, given t hat most people in the field believed melatonin acts exclusively throu gh membrane receptors. However, these new findings establish a nuclear signalling pathway for melatonin, i.e., direct ligand-induced control of target gene transcription, which most probably mediates part of th e physiological functions of the hormone. Interestingly, the very rece ntly identified first RZR/melatonin responding gene, 5-lipoxygenase, i s not expressed in the brain and is not involved in circadian rhythmic ity, but rather acts in the periphery, mainly in myeloid cells, as one of the key enzymes of allergic and inflammatory reactions. Thus, nucl ear melatonin signalling opens up a new perspective in understanding t he actions of the pineal gland hormone.