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Inhibition of glucocorticoid‐induced epidermal and dermal atrophy with KH 1060 – a potent 20‐epi analogue of 1,25‐dihydroxyvitamin D 3
Author(s) -
Gniadecki Robert,
Gniadecka Monika,
Serup Jørgen
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb17008.x
Subject(s) - betamethasone , glucocorticoid , dermis , endocrinology , chemistry , medicine , atrophy , hairless , in vivo , epidermis (zoology) , hydroxyproline , biochemistry , biology , pathology , anatomy , microbiology and biotechnology
1 The possibility of preventing and treating glucocorticoid‐induced skin atrophy with KH 1060 (the potent 20‐epi‐22‐oxa‐24a‐homo‐26,27‐dimethyl 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 topically for 7 days together with 2.5 nmol cm −2 betamethasone‐17‐valerate prevented, in a concentration‐dependent manner, the development of epidermal, dermal and total skin thinning caused by the glucocorticoid. The effect of KH 1060 on the epidermis occurred at a lower dose than on the dermis, and at doses above 1.25 pmol cm −2 KH 1060 caused epidermal 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 atrophy. 4 Radiolabelling experiments with [ 35 S]‐sulphate and [ 3 H]‐proline in vivo revealed that KH 1060 stimulated the synthesis of sulphated glycosaminoglycans and hydroxyproline in skin treated with betamethasone. 5 These findings strongly suggest that KH 1060 prevents and reverses glucocorticoid‐induced skin atrophy by stimulating epidermal proliferation and enhancing synthesis of extracellular matrix in the dermis.