Hairless And The Polyamine Putrescine Form A Negative Regulatory Loop In The Epidermis

August 2013 in “ Experimental Dermatology ”

Courtney T. Luke, Alexandre Casta, Hyun-Mi Kim, Angela M. Christiano

Hairless protein putrescine ornithine decarboxylase MYC superfamily proteins hair follicle cycling epidermal homeostasis keratinocytes epigenetic mechanisms polyamines

Studysummary This study found that Hairless (HR) and putrescine form a negative regulatory network that impacts epidermal homeostasis and hair follicle cycling, linked to the MYC superfamily's regulation of ODC expression.

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The study revealed a negative regulatory loop between the Hairless (HR) protein and the polyamine putrescine in the epidermis, impacting hair follicle cycling and epidermal homeostasis. HR regulated ornithine decarboxylase (ODC) expression through MYC superfamily proteins, while elevated putrescine levels decreased HR expression. This mutual regulation was linked to hair loss phenotypes in mouse models with altered HR or polyamine enzyme expression. The research suggested that putrescine influenced gene expression through various pathways, including epigenetic mechanisms, affecting a small number of genes in keratinocytes. These findings highlighted the complex regulatory mechanisms involving HR and polyamines, with implications for hair cycling and potentially carcinogenesis.

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research Polyamines and Hair: A Couple in Search of Perfection

30 citations , July 2010 in “Experimental Dermatology”

This article reviews the role of polyamines in hair follicle growth and discusses potential therapeutic applications but provides no new clinical results.

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21 citations , June 2009 in “Mammalian genome”

This study describes a mouse model for Marie Unna Hereditary Hypotrichosis, identifying mutations in the hairless gene that result in sparse or absent hair and cyst-like hair follicles.

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215 citations , September 2003 in “Journal of Biological Chemistry”

This study found that the hairless gene product (Hr) suppresses VDR-mediated gene activation by directly interacting with the vitamin D receptor, potentially affecting hair follicle function.

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107 citations , September 2002 in “Journal of Investigative Dermatology”

This study identified a distinct "exogen" phase in the hair cycle during which hair shedding occurs, primarily coupled with the anagen phase, rather than as part of the telogen phase.

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54 citations , May 2001 in “Journal of Investigative Dermatology”

This study suggests that increased putrescine levels may disrupt normal hair follicle development in transgenic mice, leading to hair loss and altered skin structure, yet these mice appear more resistant to skin tumorigenesis.

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20 citations , April 2000 in “Experimental dermatology”

This study observed that overexpression of the enzyme ODC in transgenic mice caused hair loss and skin changes similar to human papular atrichia, suggesting that ODC might be involved in a critical hair follicle function pathway.

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166 citations , July 1999 in “American Journal Of Pathology”

This study found that the loss of a functional hr gene in mice leads to premature and abnormal hair follicle regression, disrupting normal hair cycling and architecture.

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24 citations , June 1999 in “Mechanisms of Development”

This study found that ornithine decarboxylase expression is linked to cell proliferation and differentiation in hair follicle development and growth.

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412 citations , January 1998 in “Science”

This study identified a missense mutation in the human hairless gene associated with a rare form of recessively inherited alopecia universalis, pinpointed on chromosome 8p12.

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124 citations , July 1997 in “Journal of Biological Chemistry”

This study found that overexpression of an enzyme in transgenic mice led to distorted polyamine levels, resulting in permanent hair loss and female infertility.

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233 citations , July 1997 in “PubMed”

In this study, targeting ornithine decarboxylase overexpression to hair follicle keratinocytes in mice was sufficient to promote skin tumor development without additional tumor promoters.

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71 citations , May 1996 in “Journal of Investigative Dermatology”

This study found that overexpression of a mutated ornithine decarboxylase transgene in mice led to complete hair loss, which could be prevented or reversed with an ODC inhibitor.

research The Character 'Hairless' in the Mouse

35 citations , November 1931 in “Journal of Genetics”

Hairless mice lack fur due to a genetic mutation affecting skin response, not hormone issues.