Endocrine Abstracts

Liver X receptors α and β (NR1H3 and NR1H2) play major a role within cells and tissues involved in lipid metabolism and cholesterol homeostasis including macrophages, the liver and the small intestine. Within the skin however, the roles of LXR are less well documented, although in vitro studies using primary human keratinocytes have implemented LXR in the formation of the stratum corneum via the increase of transcription of the proteins involved in the AP-1 complex. The aim of this work was to provide a more complete synopsis of the location and function of LXR within human skin.

Using RT-PCR we have confirmed the presence of LXR α and β within human keratinocytes but have additionally identified LXRα and β mRNA in hair follicle outer root sheath keratinocytes, dermal fibroblasts, hair follicle connective tissue sheath fibroblasts and hair follicle dermal papilla fibroblasts, as well as within immortalized keratinocyte cell lines, HaCaT and N/TERT and immortalized sebocyte cell line, SZ95.

Immunohistochemistry using polyclonal and monoclonal LXR α and β antibodies detected LXR protein within cryosections of whole human skin. Expression was restricted to epidermal and outer root sheath keratinocytes and sebocytes. Western blotting confirmed the restricted pattern of protein expression within the cell populations above.

The MTT cell proliferation assay was used to quantify proliferation of keratinocytes, N/TERT and SZ95 cells following stimulation with synthetic LXR agonists TO903017 (100 nM) and GW683965 (500 nM) for 2 and 5 days, revealing highly significant decreases in cell numbers (P<0.001).

Whole extracted human hair follicles were treated with GW683965 (500 nM) for 5 days. Preliminary results have shown that growth within the treated follicles was inhibited by 28% compared vehicle treated controls.

Together these data suggest a key role for these nuclear receptors in the regulation of cellular proliferation within human skin and its glands and appendages.