title: Cutaneous glucocorticosteroidogenesis: securing local homeostasis and the skin integrity.
abstract: Human skin has the ability to synthesize glucocorticoids de novo from cholesterol or from steroid intermediates of systemic origin. By interacting with glucocorticoid receptors, they regulate skin immune functions as well as functions and phenotype of the epidermal, dermal and adnexal compartments. Most of the biochemical (enzyme and transporter activities) and regulatory (neuropeptides mediated activation of cAMP and protein kinase A dependent pathways) principles of steroidogenesis in the skin are similar to those operating in classical steroidogenic organs. However, there are also significant differences determined by the close proximity of synthesis and action (even within the same cells) allowing para-, auto- or intracrine modes of regulation. We also propose that ultraviolet light B (UVB) can regulate the availability of 7-dehydrocholesterol for transformation to cholesterol with its further metabolism to steroids, oxysterols or ∆7 steroids, because of its transformation to vitamin D3. In addition, UVB can rearrange locally produced ∆7 steroids to the corresponding secosteroids with a short- or no-side chain. Thus, different mechanisms of regulation occur in the skin that can be either stochastic or structuralized. We propose that local glucocorticosteroidogenic systems and their regulators, in concert with cognate receptors operate to stabilize skin homeostasis and prevent or attenuate skin pathology.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Tennessee, Health Science Center, Memphis, TN, USA.|Department of Medicine, Division of Rheumatology and Connective Tissue Diseases, University of Tennessee, Health Science Center, Memphis, TN, USA.
authors.forename: Andrzej T
authors.initials: AT
authors.lastname: Slominski
authors.affiliation: Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
authors.forename: Pulak R
authors.initials: PR
authors.lastname: Manna
authors.affiliation: School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA, Australia.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Tuckey
mesh_terms: D000305:Adrenal Cortex Hormones / Q000378:metabolism*; D005938:Glucocorticoids / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D012867:Skin / Q000378:metabolism*; D012879:Skin Physiological Phenomena; D014466:Ultraviolet Rays
chemical_list: D000305:Adrenal Cortex Hormones; D005938:Glucocorticoids
keywords: HPA axis; corticosteroids; metabolism; receptors; skin; steroidogenesis; stress