Glucocorticoid Inhibits Elevated Polyamine Biosynthesis in Psoriasis

• Published in: Journal of investigative dermatology Vol. 71; no. 3; pp. 177 - 181
• Main Authors: Russell, Diane H, Combest, Wendell L, Duell, Elizabeth A, Stawiski, Marek A, Anderson, Thomas F, Voorhees, John J
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.1978
• Subjects: Epidermis - enzymology; Glucocorticoids - pharmacology; Humans; Polyamines - analysis; Polyamines - biosynthesis; Polyamines - urine; Psoriasis - enzymology; Putrescine - analysis; Pyruvaldehyde - pharmacology; Spermidine - analysis; Spermine - analysis
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1111/1523-1747.ep12547095

In the genetic skin disease psoriasis, the number of Proliferating cells is 12-fold greater in lesional (involved) and 2.5-fold greater in uninvolved epidermis than in normal epidermis. Since increased polyamine biosynthesis is associated with Cell proliferation, we measured polyamine levels and the activities of the polyamine biosynthetic enzymes from biopsies of involved and uninvolved psoriatic epidermis and normal epidermis. Polyamine (putrescine, spermidine, and spermine) levels were: (1) higher in involved than in uninvolved epidermis (N = 7, P < 0.05); (2) higher in uninvolved (N = 7) than in normal (N = 8) epidermis (P < 0.02); (3) higher in urine from psoriatic patients (N = 7) than in normal (N = 8) urine (P < 0.02). The activities of ornithine decarboxylase, and both putrescine and spermidine-stimulated S-adenosyl-L-methionine decarboxylase, were 6- fold higher in involved versus uninvolved (N = 12) or normal epidermis (N = 12, P < 0.01). After 24 hr of glucocorticoid pretreatment of lesions the activities of all 3 enzymes were markedly inhibited (N = 12, P < 0.02). Methylglyoxal bis (guanylhydrazone) and α-methylor-nthine inhibited the in vitro activities of S-adenosyl-L-methionine decarboxylase and ornithine decarboxylase, respectively, from lesional psoriatic epidermis. In conclusion: (1) the number of proliferating cells in the hyperproliferative epidermis of psoriasis and the increase polyamines are correlated; (2) glucocorticoid inhibits lesional polyamine biosynthetic enzyme activity and is known to clear psoriatic lesions; (3) non-glucocorticoid inhibitors of polyamine formation such as those given above might improve psoriatic lesions; (4) the discovery of elevated polyamine biosynthesis in both uninvolved and involved epidermis may lead to a better understanding of misregulated cell proliferation in this disease.