In:
Skin Pharmacology and Physiology, S. Karger AG, Vol. 4, No. 4 ( 1991), p. 254-261
Abstract:
The purpose of these studies was to directly compare the pharmacologic effects of retinoids on cutaneous cells in vitro and in vivo. Previously, it was demonstrated that all-trans-retinoic acid stimulates the proliferation of growth-arrested human keratinocytes and fíbroblasts in culture. In the present studies, all-trans-retinoic acid was compared to three other retinoids – 13-cis-retinoic acid, P-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-napthalenyl-l-propenyl] benzoic acid (TTNPB) and M-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8,-tetramethyl-2-napthalenyl-l-propenyl] benzoic acid (meta-carboxy-TTNPB] – for growth stimulation using a cultured human squamous epithelial cell line (UM-SCC-1) and human dermal fíbroblasts. These four retinoids were also evaluated for their effects on reduction of horn-filled utriculi when topically applied to the skin of rhino mice. All-trans-retinoic acid stimulated proliferation of both fíbroblasts and epithelial cells over concentrations ranging from 0.01 to 1.0 μg/ml. In fíbroblasts, 13-cis-retinoic acid was less potent than all-trans-retinoic acid, whereas, in epithelial cells these two retinoids were equipotent. In contrast, TTNPB was more potent than all-trans-retinoic acid at stimulating the growth of both fíbroblasts and epithelial cells. The analog, meta-carboxy-TTNPB was essentially inactive as a growth stimulator of both cell types. In the rhino mouse utriculus reduction model, the rank order of potency for the retinoids was the same as that for in vitro cell growth stimulation (TTNPB 〉 all-trans-retinoic acid 〉 13-cis-retinoic acid). Meta-carboxy-TTNPB was inactive at reducing utriculi at a dose of 5,000 times the ED 〈 sub 〉 50 〈 /sub 〉 of TTNPB. In summary, the results of these studies show that the effects of retinoids on stimulating proliferation of fíbroblasts and epithelial cells correlate with their effects at reducing utriculi in the rhino mouse. Therefore, these in vitro models appear to have good relevance for studying the mechanisms of the pharmacologic effects of retinoids in vivo.
Type of Medium:
Online Resource
ISSN:
1660-5527
,
1660-5535
Language:
English
Publisher:
S. Karger AG
Publication Date:
1991
detail.hit.zdb_id:
1483572-1
detail.hit.zdb_id:
2131931-5
SSG:
15,3
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