Cellular metabolism and actions of 13-cis-retinoic acid

Retinoids (vitamin A and its derivatives) are potent substances for regulat ing the expression of many different genes within the body. The gene regula tory activities of retinoids are mediated primarily by the all-trans and 9- cis isomers of retinoic acid. Although 13-cis-retinoic acid (isotretinoin) does not have the potent gene regulatory activity of the other two isomers, it is an effective pharmacologic agent for treating a variety of dermatolo gic conditions. Because 13-cis-retinoic acid is also a naturally occurring retinoid that is present in the circulation, question is raised as to the b iochemical mechanism(s) responsible for its pharmacologic efficacy. Some of this efficacy likely arises from the ability of 13-cis-retinoic acid to un dergo isomerization to the significantly more active all-trans and 9-cis is omers; however, this does not account for all of the pharmacologic effects observed upon use of this retinoid. Sonic recent studies suggest that 13-ci s-retinoic acid may act by inhibiting the actions of enzymes that are neede d to metabolize steroids, while other recent studies indicate that 13-cis-r etinoic acid acts through membrane receptors present on the surface of cell s. At the present, it is not possible to rule out still other possible bioc hemical actions of 13-cis-retinoic acid in the body. It is clear, however, that if we are to fully understand the basis for the clinical efficacy of 1 3-cis-retinoic acid, a better understanding of such biochemical actions is needed.