Evidence is accumulating that skin can act as an independent steroidogenic

Evidence is accumulating that skin can act as an independent steroidogenic organ. system in physiological or pathological outcomes requires further studies with focus on cutaneous homeostasis formation IOWH032 of epidermal barrier antimicrobial activity and display of immune (both pro- and anti-inflammatory) properties. Keywords: Cortisol epidermal barrier dryness stress cytokines 1 Dry environment and cortisol production Recently Takei et al (1) IOWH032 using organotypic culture system have exhibited that human skin exposed to dry environment can increase the production and release of cortisol by as much as three folds in comparison to the control skin. Steroid 11β-hydroxylase (CYP11B1) the enzyme responsible for the conversion of 11-deoxycortisol to cortisol and its corresponding mRNA levels were also shown to be dramatically increased in the same experiment. Gene expression of IL-1β a cytokine involved in regulation of the epidermal barrier (2) also increased by six occasions. These changes have been partially (but significantly) reduced by isolating the skin via a water-impermeable plastic membrane. The authors further show that cortisol levels could increase to the same level as that of dry exposure when IL-1β was added to the culture media under a humid condition. They propose that IL-1β may be an important cytokine stimulating glucocorticosteroidogenesis in response to the stress of a dry environment. These results have confirmed previous observations made by IOWH032 many investigators that skin can function as an independent steroidogenic organ with the ability to produce cortisol in response to environmental stress [reviewed in IOWH032 (3 4 2 Steroidogenic activity of the skin Studies over the last two decades have well established the notion that skin is a bona fide endocrine organ of steroidogenesis capable of sensing and counteracting environmental stressors [reviewed in (5)]. Human skin cells under various conditions are able to produce crucial corticosteroids including deoxycorticosterone (DOC) 18 corticosterone and cortisol as it has been shown for the first time by Slominski and Paus groups (6-10). Human skin is also geared with all the enzymes receptors and transport proteins necessary for the production of these corticosteroids such as CYP11A1 3 CYP11B1 CYP17 CYP21A2 MC2 StAR and StAR related proteins as it has been shown for the first time in (11) and further confirmed by many investigators [reviewed in (3 12 This glucocorticoids synthesis including cortisol in the skin can proceed either from cholesterol (13 14 or from progesterone of systemic origin or through transformation of cortisone to cortisol [reviewed in (12)]. The expression of CYP11A1 have been shown not only in normal melanocytes keratinocytes and fibroblasts but also in number of tumor cells of non-cutaneous and cutaneous origin including melanomas (3 14 Although expression of CYP17A CYP21A2 CYP11B1 and of HSD11B1 have already been well documented in normal human skin and skin cells [reviewed in (3 12 we tested their expression in an extended panel of melanomas and other malignancy cells (Table 1). Surprisingly these genes are expressed at considerable levels in all melanoma lines tested (3 12 13 16 as well as in selected breast carcinomas oral squamous Foxo4 cell carcinomas osteosarcomas gliomas and leukemia cells (Table 1). This suggests that melanoma and other tumors can utilize glucocorticosteroids to modify their local environment facilitating a tumor survival in the host. Interestingly HSD11B1 has also been expressed in all tested human neonatal and adult epidermal keratinocytes melanocytes and dermal fibroblasts with expression significantly higher in intact skin and adipose tissue with the latter expression level similar to the adrenal gland (see legend to the Table 1). Table 1 Expression of steroidogenic genes in cell lines of melanoma (MM) breast carcinoma (BC) oral squamous cell carcinoma (OSCC) leukemia osteosarcoma glioma and human embryonic kidney cell line (HEK293). 3 Hypothalamic-pituitary-adrenal (HPA) axis in IOWH032 the skin Since Takei et al (1) have pointed out cutaneous HPA axis without a proper context it is important to note.