ALTERED PROLIFERATION, SYNTHETIC ACTIVITY, AND DIFFERENTIATION OF CULTURED HUMAN SEBOCYTES IN THE ABSENCE OF VITAMIN-A AND THEIR MODULATIONBY SYNTHETIC RETINOIDS

Human sebocytes maintained in medium containing delipidized serum were studied for ultrastructural characteristics, cell proliferation, lipi d synthesis, immunophenotype, and keratin expression before and after the addition of the synthetic retinoids isotretinoin and acitretin (10 (-8)-10(-5) M). Compared to the properties of sebocytes cultured in no rmal sebocyte medium (1-2 x 10(-7) M vitamin A), the use of delipidize d serum (undetectable amounts of vitamin A) resulted in prominent decr ease of i) proliferation; ii) number of intracellular lipid droplets a nd synthesis of total lipids, especially triglycerides, squalene, and wax esters; and iii) labeling with monoclonal antibodies identifying p rogressive and late-stage sebocyte differentiation. Intercellular spac es narrowed and cell-to-cell contacts were established by abundant des mosomes. Lanosterol was induced. Keratins 14, 16, 17, and 18 were upre gulated and the keratin 16: keratin 4 ratio, negatively correlating wi th sebocyte differentiation, increased. Addition of isotretinoin and a citretin exerted a biphasic effect. At concentrations less-than-or-equ al-to 10(-7) M, both compounds enhanced sebocyte proliferation and syn thesis of total lipids, especially triglycerides and cholesterol, and decreased lanosterol, keratin 16, and the keratin 16:keratin 4 ratio. In contrast, retinoid concentrations > 10(-7) M inhibited sebocyte pro liferation in a dose-dependent manner. Our findings indicate that vita min A is essential for proliferation, synthetic activity, and differen tiation of human sebocytes in vitro. Synthetic retinoids partially rei nstate the altered functions of sebocytes maintained in medium contain ing delipidized serum. In contrast to the previously shown isotretinoi n-specific response of cultured sebocytes in the presence of vitamin A , similar effects of isotretinoin and acitretin were obtained in its a bsence. This suggests different interactions of synthetic retinoids wi th vitamin A, possibly influencing their efficacy on the sebaceous gla nd.