MECHANISMS OF ANDROGEN INDUCTION OF SEBOCYTE DIFFERENTIATION

It has been difficult to induce the expected sebocyte differentiation in vitro with dihydrotestosterone (DHT). We reasoned that our culture system lacks differentiating factors, and peroxisome proliferator-acti vated receptors (PPARs) were the prime candidates. We tested PPAR acti vators informative about diverse PPAR subtypes, with and without DHT ( 10(-6) M): BRL-49653 (10(-6) M, PPAR-gamma), WY-14643 (10(-6) M, PPAR- alpha), and linoleic acid (LIN, 10(-4) M, PPAR-delta). Treatments were added in serum-free medium to cultures of rat preputial sebocytes. Co ntrol, DHT, BRL and BRL+DHT treatments caused 11, 25, 66 and 80%, resp ectively, of preputial cell colonies to differentiate into lipid-formi ng colonies (LFCs) (p<0.001). WY induced 20% and LIN over 95% LFC form ation. PPAR-gamma mRNA was identified in preputial sebocytes by the RN ase protection assay. These data suggest that differentiation of seboc ytes is transduced by PPARs and have implications for the development of new treatments for acne.