Effects of retinoids on DNA synthesis of pig epidermis: its relation to epidermal beta-adrenergic adenylate cyclase response and to epidermal superoxide dismutase activity.
It has been suggested that the epidermal beta-adrenergic adenylate cyclase response and the epidermal superoxide dismutase (SOD) activity is inversely associated with keratinocyte cell proliferation. Effects of various retinoids on the thymidine incorporation of pig epidermis were compared with their effects on the beta-adrenergic response and the SOD activity. Following 24 h incubation with synthetic retinoids (etretin and E-5166 (3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid)), thymidine incorporation of epidermis was significantly decreased. The effect of etretin was more potent than that of E-5166; the former revealed the inhibitory effect at lower concentrations than the latter. The effect of etretinate was not statistically significant. Following the 24 h incubation with the synthetic retinoids, the epidermal beta-adrenergic adenylate cyclase responses were increased. Etretin was again more potent than E-5166, while etretinate showed also little effect on the beta-adrenergic response of epidermis. Thus the inhibitory effect on the thymidine incorporation was inversely correlated with the beta-adrenergic augmentation effect among these synthetic retinoids. On the other hand, physiologic retinoids (retinol and retinoic acid) revealed no correlation between these two parameters; whereas both compounds decreased the thymidine incorporation to a similar extent, only retinoic acid revealed a marked beta-adrenergic augmentation effect. Decreased SOD activity has been observed in various hyperproliferative epidermis. The SOD activity, however, was totally unaffected by the retinoid-treatments.
Hashimoto
Y
Y
Department of Dermatology, Asahikawa Medical College, Japan.
Ohkuma
N
N
Iizuka
H
H
D017255:Acitretin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis*; D004817:Epidermis / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D005050:Etretinate / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D012176:Retinoids / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism*; D013552:Swine / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D014212:Tretinoin / Q000031:analogs & derivatives / Q000494:pharmacology; D014801:Vitamin A / Q000494:pharmacology
D012176:Retinoids; D014801:Vitamin A; D014212:Tretinoin; D005050:Etretinate; C034534:3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid; D004247:DNA; D013482:Superoxide Dismutase; D000262:Adenylyl Cyclases; D017255:Acitretin; D013936:Thymidine