Steroidogenesis in the skin: Implications for local immune functions

Abstract

The skin has developed a hierarchy of systems that encompasses the skin immune and local steroidogenic activities in order to protect the body against the external environment and biological factors and to maintain local homeostasis. Most recently it has been established that skin cells contain the entire biochemical apparatus necessary for production of glucocorticoids, androgens and estrogens either from precursors of systemic origin or, alternatively, through the conversion of cholesterol to pregnenolone and its subsequent transformation to biologically active steroids. Examples of these products are corticosterone, cortisol, testosterone, dihydrotesterone and estradiol. Their local production can be regulated by locally produced corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) or cytokines. Furthermore the production of glucocorticoids is affected by ultraviolet B radiation. The level of production and nature of the final steroid products are dependent on the cell type or cutaneous compartment, e.g., epidermis, dermis, adnexal structures or adipose tissue. Locally produced glucocorticoids, androgens and estrogens affect functions of the epidermis and adnexal structures as well as local immune activity. Malfunction of these steroidogenic activities can lead to inflammatory disorders or autoimmune diseases. The cutaneous steroidogenic system can also have systemic effects, which are emphasized by significant skin contribution to circulating androgens and/or estrogens. Furthermore, local activity of CYP11A1 can produce novel 7 -steroids and secosteroids that are biologically active. Therefore, modulation of local steroidogenic activity may serve as a new therapeutic approach for treatment of inflammatory disorders, autoimmune processes or other skin disorders. In conclusion, the skin can be defined as an independent steroidogenic organ, whose activity can affect its functions and the development of local or systemic inflammatory or autoimmune diseases.

Intracrine sex steroid synthesis and signaling in human epidermal keratinocytes and dermal fibroblasts

“…This study is not only consistent with previous work describing human skin as both a hormone target and an endocrine gland (20)(21)(22)40), but establishes that early passage (P3) primary cultures of human dermal fibroblasts and epidermal keratinocytes retain in culture the key steroidogenic proteins seen in whole skin biopsies that are required for the conversion of cholesterol to potent androgens and estrogens (Fig. 1).…”

MANAGEMENT OF ENDOCRINE DISEASE: Secondary polycystic ovary syndrome: theoretical and practical aspects

“…A fundamental prerequisite is represented by the fact that if different androgens are needed to fully define hyperandrogenemia in these women, it could be that different mechanisms may be involved in regulating the enzyme activity involved in the androgen production rate or in their metabolic clearance rate (18). In addition, although there is a consensus that increased androgen production in PCOS women is mainly dependent on hyperactivity of the ovarian theca cells, some uncertainty still remains regarding the role of adrenals and extraglandular sites (8), such as the adipose tissue and the liver and possibly the skin cell, as they express the most crucial genes of steroidogenesis and also utilize sex steroid precursors of potent androgens (19,20). This may have some relevance in explaining the presence of hirsutism in women without evidence for an altered blood androgen profile.…”

Hair cortisol detection in dairy cattle by using EIA: protocol validation and correlation with faecal cortisol metabolites

“…In spite of the clear advantages and potential applications of hair cortisol detection, several gaps need to be clarified, especially regarding the origin of the cortisol and the factors that modulate its accumulation. Some accumulation mechanisms are still incompletely understood (Henderson 1993;Cone 1996;Boumba et al, 2006) and the presence of local steroidogenesis in skin has been demonstrated (Taves et al, 2011;Slominski et al, 2013 and. As a consequence, some studies discuss the main source of cortisol accumulated in hair by highlighting the importance of local cortisol production in the final hair cortisol concentration and its different regulation from adrenal-origin cortisol (Ito et al 2005;Keckeis et al, 2012;Sharpley et al, 2012).…”