Evaluation of topical retinoids for cutaneous pharmacological activity in Yucatan microswine

The pharmacological effects of retinoids on skin have been studied primarily in test systems using small animals, such as mice and rabbits. Because of potentially significant differences in skin permeation and metabolism between small animals and humans, we have used Yucatan microswine as an alternative model for testing topical retinoids. Microswine skin resembles human skin, functionally and anatomically, more closely than most other species. In these studies, microswine skin was treated topically with retinoids for 5 consecutive days per week for 5 weeks. We found microswine epidermis to be functionally responsive to retinoids in that it undergoes hyperplasia and shows an increase in transepidermal water loss (TEWL). All-trans-retinoic acid, and its analogs, 13-cis-retinoic acid, 4-hydroxy-retinoic acid and 4-oxo-retinoic acid all caused epidermal thickening and increased TEWL. The three analogs were less potent than all-trans-retinoic acid. A synthetic retinoid, TTNPB, potently induced epidermal hyperplasia and increased TEWL, but a close structural analog, m-carboxy-TTNPB, which is also inactive on nuclear retinoic acid receptors, was without effects on microswine epidermis. These findings show that microswine are useful for evaluating the cutaneous effects of topical retinoids. This model could be of value in identifying retinoids with potential clinical activity.