INHIBITION OF GLUCOCORTICOID-INDUCED EPIDERMAL AND DERMAL ATROPHY WITH KH-1060 - A POTENT 20-EPI ANALOG OF 1,25-DIHYDROXYVITAMIN D-3

1 The possibility of preventing and treating glucocorticoid-induced sk in atrophy with KH 1060 (the potent 20-epi-22-oxa-24a-homo-26,27-dimet hyl analogue of 1,25-dihydroxyvitamin D-3) was examined in a hairless mouse model. 2 KH 1060 (0.625-6.25 pmol cm(-2) of skin) applied topica lly for 7 days together with 2.5 nmol cm(-2) betamethasone-17-valerate prevented, in a concentration-dependent manner, the development of ep idermal, dermal and total skin thinning caused by the glucocorticoid. The effect of KH 1060 on the epidermis occurred at a lower dose than o n the dermis, and at doses above 1.25 pmol cm-2 KH 1060 caused epiderm al hyperplasia. 3 KH 1060 (2.5 pmol cm(-2)) prevented the development of betamethasone-associated skin atrophy in mice during a long-term (4 weeks) treatment, and reversed established cutaneous glucocorticoid a trophy. 4 Radiolabelling experiments with [S-35]-sulphate and [H-3]-pr oline in vivo revealed that KH 1060 stimulated the synthesis of sulpha ted glycosaminoglycans and hydroxyproline in skin treated with betamet hasone. 5 These findings strongly suggest that KH 1060 prevents and re verses glucocorticoid-induced skin atrophy by stimulating epidermal pr oliferation and enhancing synthesis of extracellular matrix in the der mis.