Background and Objective: The marked efficacy of isotretinoin in the treatment of acne is undoubtedly due to its potential to inhibit sebaceous gland activity. The question arises if the anti-acne effect of new oral retinoids can be predicted by using the currently available experimental models. Methods: We reviewed the effects of various oral retinoids on sebum excretion in humans and their efficacy in acne. The human data were compared to the results obtained from in vitro and animal models. Results: Oral retinoids such as etretinate, acitretin and the so-called arotinoids were not able to inhibit the sebum production in humans and were ineffective against acne. In various animal models (i.e. sebum production in rats, flank organ size in hamsters, ear sebaceous gland size in hamster, most of these retinoids were shown to be effective. Furthermore, in addition to isotretinoin, some retinoids were able to suppress the proliferation of human sebocytes in vitro. Conclusions: The elucidation of the mechanism of action of isotretinoin on the sebocyte biology is critical for the search of more reliable models and for the discovery of new retinoids with anti-acne activity.

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