Retinoids: New Developments in Their Mechanism of Action as Related to Control of Proliferative Diseases

Abstract

Although there has been recent concern that improper use of retinoids can induce a proliferative reaction in various types of cells (10), there can be little doubt that the basic, physiological role of retinoids is to control proliferative activity in the various secretory and ductular epithelial tissues of the body. This has been known since the original classic observations of Wolbach and Howe (15) on the pathogenesis and histogenesis of vitamin A deficiency in the rat, and is nowhere better stated than in their original paper. They noted that “growth activity of (retinoid-deficient) epithelium is not diminished. On the contrary, there is convincing evidence that it is greatly augmented. In (some of the retinoid-deficient) animals, the behavior of the replacing epithelium in respect to numbers of mitotic figures and response on the part of the connective tissue and blood vessels suggests the acquisition of neoplastic properties … It is highly probable that the epithelium of gland ducts, respiratory mucosa, and genitourinary tract have secretory functions, so that we conclude that the [retinoid] deficiency results in loss of specific chemical functions of the epithelia concerned, while the power of growth becomes augmented.”