Cutaneous glucocorticosteroidogenesis: Securing local homeostasis and the skin integrity

A.T. Słomiński, P.R. Manna, Robert Tuckey

Research output: Contribution to journalArticle

44 Citations (Scopus)

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 {increment}7 steroids, because of its transformation to vitamin D3. In addition, UVB can rearrange locally produced {increment}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. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Original languageEnglish
Pages (from-to)369-374
JournalExperimental Dermatology
Volume23
Issue number6
DOIs
Publication statusPublished - 2014

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Skin
Homeostasis
Steroids
Ultraviolet Rays
Cyclic AMP-Dependent Protein Kinases
Secosteroids
Cholesterol
Cholecalciferol
Glucocorticoid Receptors
Pathology
Neuropeptides
Metabolism
Glucocorticoids
Chemical activation
Availability
Phenotype
Enzymes

Cite this

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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 {increment}7 steroids, because of its transformation to vitamin D3. In addition, UVB can rearrange locally produced {increment}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. {\circledC} 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",
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Cutaneous glucocorticosteroidogenesis: Securing local homeostasis and the skin integrity. / Słomiński, A.T.; Manna, P.R.; Tuckey, Robert.

In: Experimental Dermatology, Vol. 23, No. 6, 2014, p. 369-374.

Research output: Contribution to journalArticle

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AB - 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 {increment}7 steroids, because of its transformation to vitamin D3. In addition, UVB can rearrange locally produced {increment}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. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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