TOPICAL ALL-TRANS-RETINOIC ACID RAPIDLY CORRECTS THE FOLLICULAR ABNORMALITIES OF THE RHINO MOUSE - AN ULTRASTRUCTURAL-STUDY

Topical all-trans retinoic acid (RA) has been shown to transform the h orn-filled utriculi of the rhino mouse into normal follicles. We studi ed the early events by light and electron microscopy. Reduction in dia meters of the utriculi was quantified by image analysis of whole mount s. Topical RA at 0.05% in ethanol/propylene glycol was applied daily a nd biopsies were taken after 1, 2, 3 and 6 days of treatment. By elect ron microscopy, after 3 days of RA treatment there was a great increas e in the size and density of laminated membrane coating granules (MCGs ) which had fused to the apical membranes of the upper granular cells. Thereafter, corneocytes within the lumina of the utriculi showed fewe r desmosomes and a loss of intercellular material, accompanied by deta chment from each other. Conversion to normal follicles was complete by 6 days. In whole mounts examined after 3 days of RA, there was a 75% reduction in the mean diameter of the utriculi. These results suggest that extrusion of the contents of enlarged MCGs into the intercellular corneocyte spaces facilitated separation of corneocytes, leading to r apid shedding, perhaps through the action of desmosome-lysing protease s. The conversion to normal follicles is consistent with the establish ed role of retinoids in correcting abnormal differentiation.