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From: Kuch
Date: 5/14/2002
Time: 1:43:15 PM
Remote Name: 66.88.192.59
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Abstract TITLE: Molecular changes induced by androgens in human skin-SCID mouse model AUTHORS (ALL): Li, Wen-Hwa 1; Eisinger, Magdalena 1 INSTITUTIONS (ALL): 1. Skin Biology, Johnson&Johnson Skin Research Center, Consumer and Personal Care Group, Skillman, NJ, USA; 2. Skin Biology, Johnson&Johnson Skin Research Center, Consumer and Personal Care Group, Skillman, NJ, USA;
ABSTRACT BODY: Abstract Body: Clinical observations indicate that steroid hormones (dihydrotestosterone-DHT) and adrenal steroid (dehydroepiandosterone-DHEA) play an important role in the initiation of acne. Toward a better understanding of their mechanism of action we studied the effects of topically applied DHT or DHEA on human skin transplanted onto SCID mice. Skin of postmenopausal women was used and transplanted onto four to six weeks old male or female SCID mice. A significant increase in the sebaceous gland size (~ 4 fold) was observed within 8-12 weeks when transplanted onto male mice. In contrast, when female skin recipients were used, the sebaceous glands remained small. Measurement of sebum production by Sebutape® revealed significant sebum production in human skin grafts on male, but not on female SCID mice. Consequently, human skin grafts transplanted onto female mice were treated daily with 1% DHT or 1% and 10% DHEA for 30 days. Morphometric evaluation of such grafts revealed a 9 fold increase in the gland size in grafts treated with 1%DHT, 8.7 fold increase in the grafts treated with 1%DHEA and 13 fold increase in grafts treated with 10% DHEA. Moreover, there was a significant increase in the expression of MSH in the sebaceous glands of grafts treated with 10% DHEA, and of MC5-R in all treatment groups. Following treatment, EMA, a sebocyte differentiation marker, was expressed on all, but basal cells of the sebaceous gland, while vehicle treated controls displayed this marker only in cells approaching the sebaceous duct. Our results indicate that: 1) androgens increase cell proliferation and differentiation in the sebaceous glands and 2) MSH and its receptor (MC5-R), previously implicated in sebogenesis, may be the mediators of increased lipid production in sebaceous glands.
KUCH
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