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Effect of 1,24R‐dihydroxyvitamin D 3 on the Growth of Human Keratinocytes
Author(s) -
Matsumoto Kunio,
Hashimoto Koji,
Kiyoki Mamoru,
Yamamoto Masaru,
Yoshikawa Kunihiko
Publication year - 1990
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/j.1346-8138.1990.tb03714.x
Subject(s) - dna synthesis , cell growth , growth inhibition , calcitriol , calcitriol receptor , cell culture , cytotoxicity , keratinocyte , cytosol , chemistry , microbiology and biotechnology , receptor , vitamin d and neurology , stereochemistry , dna , biology , in vitro , biochemistry , endocrinology , enzyme , genetics
The effect of 1,24R‐dihydroxyvitamin D 3 (1,24R(OH) 2 D 3 ), a synthetic analogue of a biologically active form of vitamin D 3 (1,25‐dihydroxyvitamin D 3 , 1,25(OH) 2 D 3 ), on the growth of human keratinocytes cultured in serum‐free medium was investigated. The growth of cultured normal human keratinocytes was inhibited by 65% by 10 −8 M 1,24R(OH) 2 D 3 and by 90% by 10 −7 M 1,24(OH) 2 D 3 . It inhibited cell growth almost completely at 10 −6 M. The DNA synthesis of keratinocytes was also inhibited with 1,24R(OH) 2 D 3 by 27% at 10 −8 M, 59% at 10 −7 M, and 92% at 10 −6 M. The inhibition of cell growth and DNA synthesis were more remarkable by 1,24R(OH) 2 D 3 than by 1,25(OH) 2 D 3 . 1,24R(OH) 2 D 3 also inhibited the growth of keratinocytes derived from patients with psoriasis vulgaris; the growth inhibitory effect was again more remarkable with 1,24R(OH) 2 D 3 than with 1,25(OH) 2 D 3 . The viability and protein synthesis of keratinocytes were not affected by 1,24R(OH) 2 D 3 , suggesting that the growth inhibitory effect is due to its biological activity, not to cytotoxicity. The binding of [ 3 H]‐labeled 1,25(OH) 2 D 3 to its receptor in the cytosolic fraction of cultured keratinocytes was competitively substituted by unlabeled 1,24R(OH) 2 D 3 as well as 1,25(OH) 2 D 3 , suggesting that 1,24R(OH) 2 D 3 binds to the 1,25(OH) 2 D 3 receptor. It was found that the affinity of 1,24R(OH) 2 D 3 for the receptor was slightly higher than that of 1,25(OH) 2 D 3 . These results demonstrate that 1,24R(OH) 2 D 3 functions as a potent growth inhibitor in vitro in human keratinocytes from both normal and psoriatic epidermis, and it possesses a higher affinity for the 1,25(OH) 2 D 3 receptor in cultured human keratinocytes. The difference in affinity of 1,24R(OH) 2 D 3 for the 1,25(OH) 2 D 3 receptor correlates with its greater inhibition of keratinocyte growth than 1,25(OH) 2 D 3 . 1,24R(OH) 2 D 3 may be useful in the treatment of psoriasis.