EFFECT OF TOPICAL TRETINOIN ON NON-SUN-EXPOSED HUMAN SKIN CONNECTIVE-TISSUE - INDUCTION OF TENASCIN BUT NO MAJOR EFFECT ON COLLAGEN-METABOLISM

The effects of topical tretinoin on collagen synthesis and degradation were studied in 29 volunteers. The subjects applied 0.1% tretinoin cr eam on their non-sun-exposed abdominal skin once a day for 1 week (n = 10) (experiment 1) or twice a day for 2 weeks (n = 8) (experiment 2) or once a day for 2 months (n = 11) (experiment 3). After the treatmen ts, suction blisters were induced and aminoterminal propeptides of typ e I and III procollagens (PINP, PIIINP, respectively) (experiments 1 a nd 3) and carboxy-terminal propeptide of type I procollagen (PICP) (ex periment 2) were assayed as an index of de novo collagen synthesis by radioimmunoassays. Matrix metalloproteases 2 (MMP-2) and 9 (MMP-9) wer e assayed by the zymography method in experiment 2. In experiment 3, h istology, immunohistochemistry of type I and III procollagens, tenasci n, mRNA levels of type I collagen alpha 1-chain [alpha 1(I)], intersti tial collagenase (MMP-1), MMP-2, MMP-9 by slot-blot analysis and the l evels of alpha 1(I) collagen mRNA by a quantitative polymerase chain r eaction method were studied. The proportional area of elastic fibres v isualized in Verhoeff-stained sections was analysed by computerized di gital image analysis. The results indicated that treatment with topica l tretinoin does not markedly induce de novo synthesis of collagen in vivo or affect matrix metalloproteases. In the immunohistochemical sta inings, tenascin was increased in the papillary dermis. As it has been suggested that tretinoin could counteract the atrophogenic effect of corticoids on the dermis, the effect of a combination of betamethasone -17-valerate (once a day) and tretinoin (once a day) on the propeptide levels was also studied. Betamethasone alone caused a 60% decrease in the concentrations of PINP and PIIINP, and a similar decrease was fou nd after the combination treatment, indicating that topical tretinoin administered during short treatment periods does not counteract the in hibitory effect of a potent corticoid on collagen propeptides.