| Summary: | 碩士 === 東吳大學 === 微生物學系 === 94 === The epidermis is the most superficial layer of the skin and provides the first barrier of protection from the invasion of foreign substances into the body. The principal cells of the epidermis are called keratinocytes. Recent in vivo and in vitro studies suggest that sex steroid hormone estrogen may regulate a variety of responses of the skin, including stimulation the cell proliferation of keratinocytes. The effect of estrogen on keratinocyte’s proliferation has been suggested to be mediated through both the activation of estrogen receptor-dependent and -independent pathways. Isoflavones, a group of plant chemicals with similar structure to estrogen, are found chiefly in soy and soy products. In this study, the effects of isoflavone daidzein on primary human keratinocytes HEKa were analyzed. The results showed that both daidzein and estrogen 17 β-estradiol stimulated the proliferation of keratinocytes. The maximal growth activating effect was achieved at the concentrations of 3 nM and 1 mM for 17-beta estradiol and daidzein, respectively and was blocked by estrogen antagonist ICI182780. Via flow cytometry and RT-PCR, the presence of estrogen receptor-alpha was detected in HEKa cells. The co-administration of PI3K inhibitor wortmaninn, but not LY294002 and MEK/ERK inhibitor U0126 partially repressed the daidzein activated cell growth. However, the mRNA level of GM-CSF, whose gene expression has been suggested to be regulated through the MEK/ERK pathway, was not altered in response to estrogen or daidzein. The results of cell cycle analysis implied that daidzein promoted the progression of G1-S phase transition while estradiol promoted both the progression rates of G1-S and S-G2/M transition of HEKa cells. In summary, daidzein and 17-beta estradiol activating cell proliferation of human primary keratinocytes are most likely through similar pathways. Daidzein mainly affected keratinocyte on estrogen-like activity and is potentially decreased the effects of keratinocyte growth slowly.
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