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    The roles of hepatocyte growth factor family members in androgen-regulation of human hair growth. A comparison of the expression of hepatocyte growth factor family members, HGF and MSP, and their receptors, c-Met and RON, in isolated hair follicles from normal and androgenetic alopecia (balding) scalp.

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    PhD Thesis (6.151Mb)
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    Publication date
    2010
    Author
    Al-Waleedi, Saeed A.
    Supervisor
    Randall, Valerie A.
    Keyword
    HGF
    MSP
    c-Met
    RON
    Hair follicles
    Androgen
    Androgenetic alopecia
    PCR
    Gene microarray
    Balding
    Immunohistochemistry
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    Rights
    Creative Commons License
    The University of Bradford theses are licenced under a Creative Commons Licence.
    Institution
    University of Bradford
    Department
    Department of Biomedical Sciences
    Awarded
    2010
    
    Metadata
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    Abstract
    Androgens are the main regulators of human hair growth stimulating larger, terminal hair development e.g. beard and causing scalp balding, androgenetic alopecia. Hair disorders cause psychological distress but are poorly controlled. Androgens probably act by altering regulatory paracrine factors produced by the mesenchyme-derived dermal papilla. This study aimed to investigate paracrine factors involved in androgen-regulated alopecia, particularly hepatocyte growth factor (HGF) family members, by investigating their in vivo status. Balding and non-balding scalp hair follicles and their component tissues were isolated and analysed by molecular biological methods (reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative PCR and DNA microarray analysis), cell culture and immunohistochemistry. Scalp follicles expressed a range of paracrine messenger genes. The dermal papilla, cultured dermal papilla cells and dermal sheath expressed several HGF family genes, while matrix cells only produced the receptor RON suggesting autocrine roles for HGF and MSP, but a paracrine route only for MSP. Comparing balding and non-balding follicles from the same individuals revealed the expected reduction in several keratin and keratin-related protein genes supporting this approach's validity. There were also significant differences in paracrine factors previously implicated in androgen action by in vitro studies. Several factors believed to increase during androgen stimulation of larger, darker follicles, e.g. IGF-I and SCF, were lowered in balding follicles, while putative inhibitory factors, e.g. TGFß-1, were increased. HGF and MSP and their receptors, c-Met and RON, were significantly reduced. These results increase our understanding of androgen action in human hair follicles; this could lead to better treatments for hair disorders.
    URI
    http://hdl.handle.net/10454/5271
    Type
    Thesis
    Qualification name
    PhD
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